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Biomedical subjects

O Nagata

Publications and source records attributed to O Nagata.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Anesthetic management of a patient with Alzheimer's disease].

We gave anesthesia to a 60-year-old female patient in stage III (end stage) of Alzheimer's disease for sigmoidectomy. She had myoclonus and parkinsonism and it was not possible to communicate with her verbally. After induction of anesthesia with thiopental, she had a catheter inserted into epidural space. Without endotracheal intubation, anesthesia was maintained with nitrous oxide, oxygen and isoflurane under spontaneous ventilation supplemented with mepivacaine from the epidural catheter. No muscle relaxant was used. Recovery from the anesthesia was uneventful. No complication was observed during anesthesia and postoperatively.

Adenocarcinoma↗
PubMed1992

Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor.

We measured dose-response curves for carbachol stimulation of phosphatidyl inositol (PI) turnover with mutants of the Hm1 muscarinic cholinergic receptor having various deletions from amino acids 219 to 358 of the large third intracellular (i3) loop (208 to 366). These deletions had only small or no effects on the ability of Hm1 transfected into HEK 293 cells to stimulate PI turnover. This result indicates that only small regions of 9 to 11 amino acids adjacent to trans-membrane domains (TMDs) 5 and 6 can be directly involved in G protein coupling. Point mutations were constructed to test the role of charged amino acids in these junctions. A triple point mutation of Hm1 (E214 A/ E216K/ E221 K), which mimics the charge distribution in Hm2 (negatively coupled to cAMP) over the first 14 amino acids of i3, and a double point mutation in the N terminal junction, K359A/K361A, both failed to affect carbachol stimulated PI turnover. Therefore, charge distribution in the loop junctions appears to play a minor role in G protein coupling of Hm1 in HEK 293 cells.

Amino Acid Sequence↗
PubMed1992

Simultaneous determination of a new gastrointestinal prokinetic agent (HSR-803) and its metabolites in human serum and urine by high-performance liquid chromatography using automated column-switching.

A method based on high-performance liquid chromatography using column-switching is described for the simultaneous determination of HSR-803 and its metabolites in human serum and urine. The system uses a six-port valve with a Nucleosil CN pre-column for on-line sample clean-up, and direct injection of samples. The limits of quantitation in serum and urine were 5 and 20 ng/ml for HSR-803 and 50 and 200 ng/ml for the metabolites, respectively. The coefficients of variation for the intra- and inter-day accuracies were between 0.8 and 7.1% for each compound. This method was applied to the pharmacokinetic studies in humans after oral administration of HSR-803.

Benzamides↗
PubMed1990

[A serous cystadenoma of the ovary of borderline malignancy with a fifteen-year history. A case report].

A case of a serous cystadenoma of a ovary of borderline malignancy is reported. Sixteen years earlier, the patient had undergone an exploratory laparotomy because of ovarian tumor, and the histologic diagnosis had been a serous cystadenocarcinoma. Postoperative chemotherapy was not effective and drainage of the tumor fluid had been performed for 15 years, with the estimated drainage volume estimated to have reached, 1,000 1. Gradual malnutrition and marked tumor growth then become apparent. A reevaluation of the initial histologic slides and her clinical course strongly suggested a serous cystadenoma of borderline malignancy. Thus a tumor resection, a bilateral salpingo-oophorectomy, and a hysterectomy was performed. A histologic diagnosis of a resected specimen confirmed a serous cystadenoma of borderline malignancy and the histologic features were quite similar to those of the initial biopsy specimens. The patient is living well postoperatively for 8 months without postoperative chemotherapy.

Adult↗
PubMed1989

Degradation kinetics of (+/-)-4'-ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HY-770) and structure-stability relationship among its analogues in aqueous solution.

The kinetics and pathways for degradation of (+/-)-4'-ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HY-770; 1), a newly developed muscle-relaxing agent, and its analogues were studied in aqueous solution at 50 degrees C, ionic strength 0.5 M, and pH 8.0-12.0. Compound 1 and its four analogues followed pseudo-first-order degradation kinetics at constant pH and temperature. From the analysis of the pH degradation-rate profiles, it is evident that specific hydroxide ion-catalyzed degradations of ionized and un-ionized species occur for 1 and its structural analogue, 3'-fluoro-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HN-961; 5). The hydroxide ion-catalyzed degradation of the ionized species was found to be 100 times faster than that of the un-ionized species and to be the major process at pH less than 9.0. On the contrary, 1 was extremely stable in 0.5 M HCl at 50 degrees C, suggesting that the hydronium ion-catalyzed degradation and the spontaneous degradation of the ionized species is negligible. The Arrhenius plot for the degradation of 1 at 35-50 degrees C and pH 9.0 showed that the apparent energy of activation was 22.0 kcal/mol. The degradation rates of the five structural analogues were significantly dependent on the electron withdrawing effect of the benzene substituents of the molecule.

Boric Acids↗
PubMed1989

Serum protein binding of lomefloxacin, a new antimicrobial agent, and its related quinolones.

The serum protein binding of lomefloxacin (LFLX), a new quinolone (pyridonecarboxylic acid), and its related analogues was studied by an ultrafiltration technique. The extent of binding of quinolones was independent of the concentration of quinolones below 100 micrograms/mL in rat serum; but, above this concentration, the binding decreased with increased drug concentration in the case of nalidixic acid and analogue 3. The extent of binding in rat serum differed widely among the quinolones examined [i.e., from 15% (norfloxacin) to 84% (nalidixic acid) at concentrations of 0.4-10.0 micrograms/mL]. Lomefloxacin was bound to serum proteins to the extent of 28.1, 20.1, and 20.6% in the sera of rats, dogs, and humans, respectively. The binding of nalidixic acid with rat serum albumin, which was very similar to that in rat serum, was concentration dependent. Some quinolone derivatives with a piperazinyl group or a relatively large-sized substituent at the 7-position exhibited a percentage unbound of approximately 70-80%, while some derivatives with small-sized substituents gave a low percentage unbound of 20-30%. This suggests that there is a steric effect of the substituents at the 7-position of quinolones on their binding characteristics with serum proteins. The results of the present study indicate that quinolones bind mainly with albumin among serum proteins and that the remarkable difference of the extent of binding of quinolone analogues is related to the size of the substituent at the 7-position of the molecule, possibly due to its steric effect.

Animals↗
PubMed1988

Enterohepatic circulation of NY-198, a new difluorinated quinolone, in rats.

Enterohepatic circulation of NY-198 in rats was studied. NY-198 glucuronide in the bile was rapidly hydrolyzed to NY-198 by the intestinal contents. Hydrolyzed and parent NY-198 in the bile were reabsorbed from the intestine. The amount of NY-198 in enterohepatic circulation was 59.8% of that excreted in the bile.

Animals↗
PubMed1988

Inhibitory effects of quinolone antibacterial agents on gamma-aminobutyric acid binding to receptor sites in rat brain membranes.

The specific binding of 3H-labeled gamma-aminobutyric acid ([3H]GABA) to synaptic plasma membranes from rat brains was inhibited by various quinolonecarboxylic acid derivatives (quinolones), and these inhibitions were concentration dependent. The binding of [3H]muscimol to GABAA sites was also inhibited. These inhibitory potencies differed widely among the quinolones examined. The Dixon plots showed that a newly developed difluorinated quinolone, NY-198 [1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid hydrochloride], competitively inhibits the receptor bindings of [3H]GABA and [3H]muscimol. In conclusion, our findings suggest that the inhibition of GABA binding to receptors (including uptake sites) in the brain may be involved in the induction of epileptogenic neurotoxicities by quinolones.

Animals↗
PubMed1988

Entry of the new quinolone antibacterial agents of ofloxacin and NY-198 into the central nervous system in rats.

The present study describes quantitatively the pharmacokinetics of the antibacterial agents, ofloxacin and NY-198 (quinolonecarboxylic acid derivatives), in the central nervous system in rats by physiological modeling of the penetration, distribution and sequestration processes. The stimulation curves corresponded well with the observed concentrations in the cerebrospinal fluid (CSF) and various brain regions after intravenous bolus administration. The estimated cerebrovascular diffusion clearances were considerably small compared with reported serum flow rates and similar among the brain parenchymal tissues examined. The distribution volume of each drug in each brain region was almost the same as the brain extracellular space (15 to 25% of the wet weight). It was also found that the Kp values of these drugs were similar among the various brain regions. These lines of evidence suggest that the antibacterial agents, ofloxacin and NY-198, localized only in the brain extracellular space and exhibited little region-specificity in distribution into the brain. Moreover, it was suggested from unexpectedly low CSF: serum concentration ratios after intravenous administration that these quinolones, which once diffused into CSF, could be sequestrated from CSF to blood via some transport system.

Animals↗
PubMed1986

Simulation analysis of excitation conduction in the heart: propagation of excitation in different tissues.

The normal excitation and conduction in the heart are maintained by the coordination between the dynamics of ionic conductance of each cell and the electrical coupling between cells. To examine functional roles of these two factors, we proposed a spatially-discrete model of conduction of excitation in which the individual cells were assumed isopotential. This approximation was reasoned by comparing the apparent space constant with the measured junctional resistance between myocardial cells. We used the four reconstruction models previously reported for five kinds of myocardial cells. Coupling coefficients between adjacent cells were determined quantitatively from the apparent space constants. We first investigated to what extent the pacemaker activity of the sinoatrial node depends on the number and the coupling coefficient of its cells, by using a one-dimensional model system composed of the sinoatrial node cells and the atrial cells. Extensive computer simulation revealed the following two conditions for the pacemaker activity of the sinoatrial node. The number of the sinoatrial node cells and their coupling coefficients must be large enough to provide the atrium with the sufficient electric current flow. The number of the sinoatrial node cells must be large so that the period of the compound system is close to the intrinsic period of the sinoatrial node cell. In this simulation the same sinoatrial node cells produced action potentials of different shapes depending on where they were located in the sinoatrial node. Therefore it seems premature to classify the myocardial cells only from their waveforms obtained by electrical recordings in the compound tissue. Second, we investigated the very slow conduction in the atrioventricular node compared to, for example, the ventricle. This was assumed to be due to the inherent property of the membrane dynamics of the atrioventricular node cell, or to the small value of the coupling coefficient (weak intercellular coupling), or to the electrical load imposed on the atrioventricular node by the Purkinje fibers, because the relatively small atrioventricular node must provide the Purkinje fibers with sufficient electric current flow. Relative contributions of these three factors to the slow conduction were evaluated using the model system composed of only the atrioventricular cells or that composed of the atrioventricular and Purkinje cells. We found that the weak coupling has the strongest effect. In the model system composed of the atrioventricular cells, the propagation failure was not observed even for very small values of the coupling coefficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Atrioventricular Node↗
PubMed1985

Absorption, excretion and metabolism of tiquizium bromide in dogs, and relationship between pharmacological effect and plasma levels of unchanged drug.

The disposition of 14C-tiquizium bromide was investigated in dogs after oral administration and i.v. administration. After oral administration, max. blood concn. of radioactivity were obtained from one to three hours after dosing. The half-lives of terminal phase were 7.1 h (i.v.) and 9.4-12.0 h (p.o.). The relative bioavailability was 26%. The urinary excretion in three days was 24% (i.v.) and 5-9% (p.o.). The most important mechanism of biotransformation was hydroxylation in the 5-position of the thiophene ring, and glucuronides of the isomeric hydroxylated products of tiquizium bromide were found in urine. The time-course of the inhibitory effect of tiquizium bromide on stomach contraction correlated well with the plasma levels of unchanged drug after intraduodenal administration.

Administration, Oral↗