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Biomedical subjects

O Nagata

Publications and source records attributed to O Nagata.

At least 37 records · Page 2Linked to original sources
PubMed2000

Characterization of the endothelin receptor subtypes in human prostate.

Endothelin (ET) receptor subtypes in human prostate with benign prostatic hyperplasia were investigated by binding and functional studies. In the displacement experiment, LU224332 [endothelin-A/-B (ET(A)/ET(B)) nonselective antagonist] competed for [125I]ET-1 binding with a monophasic curve. On the other hand, LU135252 (ET(A)-selective antagonist) and sarafotoxin S6c (S6c, ET(B)-selective agonist) competed for [125I]ET-1 binding with shallow and biphasic curves. The analysis of the displacement curves for LU135252 and S6c showed that both ET(A) and ET(B) subtypes coexist but that ET(A) is the dominantly expressed receptor. In human prostate strips, 10 microM of both LU135252 and LU224332 strongly inhibited the contractile response to ET-1 with equal potency. However, 10 microM of BQ788 (ET(B)-selective antagonist) did not show a clear inhibition. S6c also produced a contractile response, which was potently inhibited by LU224332 or BQ788, and slightly suppressed by LU135252. These results suggest that in human prostate both ET(A) and ET(B) subtypes are functional receptors mediating contraction, but that ET-1-mediated contractions are predominantly mediated by activation of dominant receptor subtype, ET(A).

Aged↗
PubMed2000

Calcium polycarbophil, a water absorbing polymer, increases bowel movement and prevents sennoside-induced diarrhea in dogs.

The effects of calcium polycarbophil (CP), a water-absorbing polymer, on bowel movement were examined in comparison with known laxatives and anti-diarrheal agents in dogs, a species that resembles humans for stool output. CP increased stool frequency, fecal water content and fecal weight in a dose-dependent manner, but did not induce diarrhea. Sennoside and carboxymethylcellulose sodium (CMC-Na) increased fecal water content and induced diarrhea at lower doses than that which enhanced stool frequency. Trimebutine decreased stool frequency, fecal weight and fecal water content, resulting in inhibition rather than stimulation of defecation. In sennoside-induced diarrhea, loperamide and CP improved stool consistency and this was accompanied by reduced fecal moisture and frequency of diarrhea. In contrast, CMC-Na aggravated stool consistency with increased fecal water content and frequency of diarrhea, and trimebutine had little noticeable effect apart from reducing fecal weight. Our results show that CP has both laxative and anti-diarrheal effects in dogs and differed from conventional laxatives and anti-diarrheal agents. CP may be a suitable agent for treatment of idiopathic constipation, secretory diarrhea and irritable bowel syndrome with alternating constipation and diarrhea and with either predominating in terms of less side effects such as diarrhea or constipation.

Acrylic Resins↗
PubMed2000

The involvement of flavin-containing monooxygenase but not CYP3A4 in metabolism of itopride hydrochloride, a gastroprokinetic agent: comparison with cisapride and mosapride citrate.

The goals of the present study were to identify the enzyme responsible for metabolism of itopride hydrochloride (itopride) and to evaluate the likelihood of drug interaction involving itopride. In human liver microsomes, the involvement of flavin-containing monooxygenase in N-oxygenation, the major metabolic pathway of itopride, was indicated by the following results: inhibition by methimazole and thiourea, heat inactivation, and protection against heat inactivation by NADPH. When the effects of ketoconazole on the metabolism of itopride, cisapride, and mosapride citrate (mosapride) were examined using human liver microsomes, ketoconazole strongly inhibited the formation of the primary metabolites of cisapride and mosapride, but not itopride. Other cytochrome P450 (CYP) 3A4 inhibitors, cimetidine, erythromycin, and clarithromycin, also inhibited the metabolism of cisapride and mosapride. In an in vivo study, itopride (30 mg/kg), cisapride (1.5 mg/kg), or mosapride (3 mg/kg) was orally administered to male rats with or without oral pretreatment with ketoconazole (120 mg/kg) twice daily for 2 days. The ketoconazole pretreatment significantly increased the area under the serum concentration curve and the maximum serum concentration of cisapride and mosapride but had no significant effect on the pharmacokinetics of itopride. In addition, itopride did not inhibit five specific CYP-mediated reactions of human liver microsomes. These results suggest that itopride is unlikely to alter the pharmacokinetics of other concomitantly administered drugs.

Administration, Oral↗
PubMed2000

[Anesthetic management for MIDCAB using the target controlled infusion and the bispectral index].

We report our experience in using the target controlled infusion (TCI) of propofol combined with the bispectral index (BIS) monitoring for anesthetic management of minimally invasive direct coronary artery bypass (MIDCAB) in a 43-year-old-male patient with angina pectoris. After premedication, the patient was connected to the monitor with electrodes for BIS monitor. Then, anesthesia was induced with fentanyl and propofol using TCI technique. When blood concentration of propofol reached 4 micrograms.ml-1, the trachea was intubated. Before starting the operation, we evaluated the relationship between blood concentration of propofol and the value of BIS, and the standard maintenance concentration of propofol was set at 3 micrograms.ml-1. When the concentration of propofol was 3 micrograms.ml-1, the value of BIS was about 60. Anesthesia was maintained with nitrous oxide and oxygen and continuous infusion of propofol using TCI technique. When necessary, we gave additional injection of fentanyl and vecuronium bromide. Furthermore, diltiazem was infused continuously for cardiac rate control, as well as infusion of nicorandil, nitroglycerine for prevention of coronary artery spasms, and prostaglandin. After the operation, the patient was alert in 8 minutes and we could extubate in 12 minutes. The use of TCI combined with BIS monitoring for maintenance of anesthesia for MIDCAB is useful and safe.

Adult↗
PubMed1999

Sensitive assay of trimethylamine N-oxide in liver microsomes by headspace gas chromatography with flame thermionic detection.

To compare the trimethylamine N-oxygenase activity of liver microsomes from house musk shrew (Suncus murinus) and rat, a sensitive method for the quantitation of trimethylamine (TMA) N-oxide was developed using gas chromatography with flame thermionic detection. The limit of quantification was 0.5 microM and the calibration curve was linear at least up to 5 microM in incubations containing liver microsomal preparations from Suncus. The intra-day RSD values ranged from 10.4 to 12.8 at 0.5 microM and from 3.5 to 6.7 at 5 microM. The inter-day RSD values were 11.6 and 6.5 at 0.5 and 5 microM, respectively. This method provides a sensitive assay for TMA N-oxygenase activity in liver microsomes. Using this method we found that Suncus was capable of N-oxidizing trimethylamine at a very slow rate.

Animals↗
PubMed1999

Peripheral nerve conduction recorded by a micro gradiometer system (micro-SQUID) in humans.

We developed a new multi (twelve) -channel gradiometer system with the smallest and highest quality superconducting quantum interference device (micro-SQUID). A very small distance (3.80 mm) between the sensor coils and the skin provides quite high spatial resolution. The actual whole image of the sensory nerve action fields (NAF) of the human median nerve at the wrist were successfully recorded following digital nerve stimulation by using the micro-SQUID. The NAF showed the biphasic waveform at each of the 12 channels, and the isomagnetic field map clearly showed the moving quadrupole pattern. The quadrupole comprised a dipole for depolarization followed by another dipole with the opposite direction for repolarization. The polarized length of the nerve obtained by reconstructing the magnetic field maps was approximately 17 cm, and the magnetic field complex moved along the nerve from the distal to the proximal part of the wrist at 58.7 m/s.

Adult↗
PubMed1999

Binding and functional characterization of alpha1-adrenoceptor subtypes in the rat prostate.

The alpha1-adrenoceptor subtypes of rat prostate were characterized in binding and functional experiments. In binding experiments, [3H]tamsulosin bound to a single class of binding sites with an affinity (pKD) of 10.79+/-0.04 and Bmax of 87+/-2 fmol mg(-1) protein. This binding was inhibited by prazosin, 2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride (WB4101), 5-methylurapidil, alpha-ethyl-3,4,5,-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amin o)-propyl)benzeneacetonitrile fumarate (HV723) and oxymetazoline with high efficacy, resulting in a good correlation with the binding characteristics of cloned alpha1a but not alpha1b and alpha1d-adrenoceptor subtypes. In functional studies, noradrenaline and oxymetazoline produced concentration-dependent contractions. These contractions were antagonized by tamsulosin, prazosin, WB4101 and 5-methylurapidil with an efficacy lower than that exhibited by these agents for inhibition of [3H]tamsulosin binding. The relationship between receptor occupancy and contractile amplitude revealed the presence of receptor reserve for noradrenaline, but the contraction induced by oxymetazoline was not in parallel with receptor occupation and developed after predicted receptor saturation. From these results, it is suggested that alpha1A-adrenoceptors are the dominant subtype in the rat prostate which can be detected with [3H]tamsulosin, but that the functional subtype mediating adrenergic contractions has the characteristics of the alpha1L-adrenoceptor subtype, having a lower affinity for prazosin and some other drugs than the alpha1A-adrenoceptor subtype.

Acetonitriles↗
PubMed1999

Anaesthetic management of two paediatric patients with Hecht-Beals syndrome.

We undertook the anaesthetic management of two children with Hecht-Beals syndrome for orthopaedic surgery under general anaesthesia. Both patients had arachnodactyly, kyphoscoliosis, and multiple congenital joint contractures, but limited mandible excursion was not obvious preoperatively in either, although mental retardation made it difficult for them to cooperate with mouth examination. They had no apparent difficulties with their mouths in daily activities. The anaesthesia records of one patient showed that intubation had been difficult in an earlier procedure. The other patient also had a history of difficult intubation, with slight tearing of the corners of her mouth during an intubation procedure. During slow induction of general anaesthesia with sevoflurane, face mask ventilation was easily performed. We attempted to visualize the larynx under anaesthesia with muscle relaxation, but we were unsuccessful because of the limited mouth opening. After several trials, blind oral intubations were fortunately successful in both patients. There were no postoperative problems with the airway.

Anesthesia, General↗
PubMed1999

Carrier-mediated lung distribution of HSR-903, a new quinolone antibacterial agent.

HSR-903 [(S)-(-)-5-amino-7-(7-amino-5-azaspiro[2. 4]hept-5-yl)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid methanesulfonate] is a newly synthesized quinolone with a potent antibacterial activity and a low toxicity. The lung concentration of unchanged HSR-903 was about nine times higher than that in plasma after oral administration (5 mg/kg) in rats. In comparative studies, HSR-903 was accumulated more efficiently than levofloxacin, ciprofloxacin, and lomefloxacin in rat lung. To clarify the mechanism of the specific distribution of HSR-903 into the lung, the uptake of [14C]HSR-903 was studied using isolated rat lung cells and an isolated rat lung perfusion technique. Initial uptake of HSR-903 by isolated lung cells was temperature dependent, saturable, stereospecific, and Na+ and Cl- dependent. The Hill coefficients (1. 90 for Na+ and 1.13 for Cl-) suggest that two Na+ and one Cl- are associated with the transport of one HSR-903 molecule. The uptake of HSR-903 was inhibited by other quinolone antibacterial agents, grepafloxacin, and sparfloxacin. The extraction ratio of HSR-903 in isolated lung perfusion was temperature dependent and saturable. These findings suggest that HSR-903 is taken up by the lung cells via a carrier-mediated transport mechanism, resulting in a concentrative distribution into the lung.

Algorithms↗
PubMed1999

[Success rate of anesthesia induction using target-controlled infusion of propofol with fentanyl].

Twenty-one patients were studied to compare the success rate of anesthesia induction using target-controlled infusion of propofol with and without fentanyl. All patients were premedicated with atropine 0.5 mg and hydroxyzine 25-50 mg. Five minutes after intravenous administration of fentanyl 2 micrograms.kg-1, patients were given infusions of propofol designed to achieve target blood concentrations of 3 micrograms.kg-1. Loss of verbal contact was regarded as successful induction. The success rate of anesthesia induction within three minutes of achieving the target concentration was 90%. Pain on injection and reduction in blood pressure were infrequent. Selecting a target concentration of 3 micrograms.kg-1 with fentanyl 2 micrograms.kg-1 can be expected to successfully induce anesthesia in the majority of patients without major hemodynamic side effects and pain on injection.

Adult↗
PubMed1999

Efflux transport of a new quinolone antibacterial agent, HSR-903, across the blood-brain barrier.

The distribution of HSR-903, a new quinolone antibacterial agent, to the brain after i.v. administration to rats was low compared with that to other tissues. The blood-brain barrier permeability to HSR-903 determined by the brain perfusion method was low, and increased nonlinearly with increasing concentration of HSR-903 in the perfusate. When the brain-to-plasma concentration ratio (Kp, brain) was measured in mdr1a gene-knockout mice, the value was 8 times higher than that in normal mice. The uptake of [14C]HSR-903 by multidrug-resistant K562/ADM cells, which express P-glycoprotein (P-gp), was significantly lower than that by the drug-sensitive parent K562 cells. In addition, the uptake of [14C]HSR-903 by K562/ADM cells was significantly increased in the presence of cyclosporin A and ATP-depleting agents. These observations support the idea that P-gp participates in HSR-903 efflux from the brain. The steady-state uptake of HSR-903 by a monolayer of primary cultured bovine brain capillary endothelial cells was increased in the presence of several quinolone antibacterial agents or anionic compounds, such as 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, and in bicarbonate ion-free medium, as well as by P-gp inhibitors (cyclosporin A and quinidine). These results suggested that the efflux of HSR-903 proceeds at least partly via an anion-sensitive efflux transport mechanism as well as via P-gp. In conclusion, the low brain distribution of the new quinolone antibacterial agent HSR-903 can be ascribed to multiple efflux mechanisms including P-gp and an unidentified anion-sensitive transporter operating in the brain capillary endothelial cells that constitute the blood-brain barrier.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

[Relationship between cardiac output and PETco2 as well as Paco2 during high-dose fentanyl anesthesia].

We investigated the relationship between cardiac output and PETCO2 as well as blood PCO2 in 10 patients undergoing cardiac surgery of long duration under high-dose fentanyl anesthesia. After anesthetic induction, the minute ventilation was kept constant at 10 ml.kg-1 x 10 cycles.min-1 and a pulmonary artery catheter was inserted. PETCO2, PaCO2 and cardiac index (CI) were measured simultaneously. PaCO2 was corrected for body temperature, and alveolar dead space-to-tidal volume ratio was calculated as VD/VTalv = (PaCO2-PETCO2)/PaCO2. After body, temperature became stabilized, the measurements were started and repeated every 10 to 20 minutes during the prebypass period. One hundred and eight sets of data were taken from 10 patients. PETCO2 correlated positively with CI. Similarly, PaCO2 correlated positively with CI, but VD/VTalv, did not correlate with CI. PETCO2 correlated closely and positively with PaCO2, but it correlated negatively and only marginally with VD/VTalv. When examined in individual patients, PaCO2 correlated positively with PETCO2 in all patients, while VD/VTalv correlated negatively with PETCO2 only in 3 patients. By multiple regression analysis, VD/VTalv change accounted for only 22.3 +/- 15.0% of PETCO2 change, while PACO2 or PaCO2 change accounted for 77.6 +/- 15.0% of PETCO2 change. Decreased CI was associated with decreased CO2 delivery from the tissue to the lung (DCO2) and PaCO2 decreased with decreasing DCO2. Decreased CI was also associated with decreased oxygen uptake (VO2), and PaCO2 decreased with decreasing VO2. A decrease in CI resulted in an increase in VA/Q, and PaCO2 decreased when VA/Q increased. PETCO2 decreased when cardiac output decreased. A decrease in PACO2 explained the decrease in PETCO2 better than an increase in VD/VT did. Decreased cardiac output might cause hypocapnia through decreased CO2 delivery to the lung, decreased CO2 production and/or increased ventilation-to-perfusion ratio.

Adult↗
PubMed1998

[The duration of action of vecuronium is unchanged when administered with propofol].

We examined the difference in the duration of action of vecuronium injected through a venous line infused with propofol and the duration of vecuronium infused into another venous line without propofol, in order to investigate the interaction between vecuronium and propofol within the intravenous lines. The subjects of the study are 8 patients, (ASA grade 1 or 2, aged from 20 to 50 years, 6 males and 2 females), who had undergone elective operations under general anesthesia. The mean duration of action of vecuronium injected through the venous line infused with propofol was 32.3 +/- 9.0 (min), while that for vecuronium injected through the venous line without propofol was 32.1 +/- 8.6 (min). There was no significant difference in the duration of action of vecuronium between the two conditions. We conclude that since vecuronium can be injected through the venous lines infused with propofol without interaction, there is no need for an additional venous line without propofol when vecuronium is administered under propofol anesthesia.

Adult↗
PubMed1998

Hepatobiliary transport kinetics of HSR-903, a new quinolone antibacterial agent.

HSR-903 is a newly synthesized quinolone antibacterial agent with low toxicity. The biliary and urinary excretion of unchanged HSR-903, its R-isomer, and their glucuronides was determined after iv bolus administration (5 mg/kg) to normal Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic mutant rats (EHBR). The values for the biliary excretion clearance of HSR-903 and its glucuronide in EHBR were decreased to approximately 40 and 2% of those in SDR, respectively, whereas the values for the urinary excretion clearance of HSR-903 and its glucuronide were comparable in SDR and EHBR. The biliary excretion clearance values for the R-isomer and its glucuronide were approximately 3 times greater than those for HSR-903. These results demonstrated that the enantiomers of HSR-903 and their conjugates were excreted into bile in a stereospecific manner. The hepatic uptake of [14C]HSR-903 in vivo was evaluated by means of integration plot analysis. The results indicated that the hepatic uptake of [14C]HSR-903 was very fast and was blood flow-limited. To clarify the mechanism of excretion of HSR-903 into bile, the uptake and efflux of [14C]HSR-903 were studied using isolated hepatocytes from SDR and EHBR. The initial uptake of HSR-903 by hepatocytes was temperature-dependent, saturable, and stereospecific. Unlabeled HSR-903 (S-isomer), the R-isomer, grepafloxacin, and sparfloxacin significantly inhibited the uptake of [14C]HSR-903. The efflux of [14C]HSR-903 from hepatocytes from EHBR was significantly slower than that from hepatocytes from SDR. The addition of sodium azide or bromosulfophthalein reduced the efflux of [14C]HSR-903. These results demonstrate that HSR-903 is actively excreted into bile via the canalicular multispecific organic anion transporter, which is deficient in EHBR.

Animals↗
PubMed1998

[Evaluation of estimated blood concentration of propofol on wake-up using "ConGrase", a software to control the syringe pump for propofol infusion].

We developed a software to control a Graseby 3500 syringe pump for propofol infusion through the serial port of Apple Macintosh/Power-Macintosh computer. This software, "ConGrase", was developed with Metrowerks CodeWarrior Professional (CWP 1) and PowerPlant framework using C++. ConGrase communicates with the syringe pump at least every three seconds, and calculates the estimated blood concentration (EBC) of propofol based on the amount of propofol actually infused by applying either the Euler or Runge-Kutta method using the three-compartment pharmacokinetic model. The parameter sets reported by Gepts et al. are used. ConGrase was released at the 44 th Annual Meeting of the Japan Society of Anesthesiology, and is distributed freely. The mean and S.D. of the emergence EBC calculated by ConGrase were 1.22 micrograms.ml-1 and 0.16 microgram.ml-1, respectively. These values are almost the same as values already reported outside Japan. The necessary wake-up time can be calculated with this estimated concentration. With this system, anesthetists can control the EBC at the required level and avoid long delays before the patients wake up after anesthesia.

Adolescent↗
PubMed1997

Odorant evoked magnetic fields in humans.

We investigated the olfactory evoked magnetic fields (OEFs) in 14 normal subjects. Pulses of odorant air containing amyl acetate or phenethyl alcohol, and odorless air were administered to the subject through a nasal tube. A clear and consistent OEF component, 1M, was identified in all subjects, and a second component, 2M, was detected in seven subjects, but no consistent component was identified in response to the odorless air. The peak latencies of the 1M and 2M components were approximately 320 and 630 ms, respectively. The waveforms produced by the odorless air were subtracted from the waveforms produced by the odorant air to obtain the 'subtraction' waveform, which indicated the 1M and 2M component more clearly. Their equivalent current dipoles (ECDs) were estimated in the regions around the Sylvian fissure symmetrically in both hemispheres. Therefore, these areas are proposed to be involved in olfactory perception in humans.

Adult↗
PubMed1997

In-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae with quinolone resistance-associated alterations in GyrA and ParC.

The in-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, was tested against 51 clinical Neisseria gonorrhoeae isolates in comparison with ciprofloxacin, levofloxacin and sparfloxacin. The MICs of HSR-903 for 11 isolates with alterations in both GyrA and ParC, for 19 isolates with alterations only in GyrA and for 21 isolates without alterations in either GyrA or ParC ranged from 0.03 mg/L to 1.0 mg/L (MIC90 = 0.25 mg/L), from 0.03 mg/L to 0.5 mg/L (MIC90 = 0.125 mg/L) and from < or = 0.001 mg/L to 0.008 mg/L (MIC90 = 0.004 mg/L), respectively. Levofloxacin and ciprofloxacin were the least active of the four quinolones tested, particularly against the mutant strains. Sparfloxacin was more active, but HSR-903 exhibited the most potent in-vitro activity against the clinical N. gonorrhoeae isolates, including those harbouring quinolone-resistance-associated alterations in GyrA and ParC.

Anti-Infective Agents↗