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A Koshiro

Publications and source records attributed to A Koshiro.

At least 19 recordsLinked to original sources
PubMed1997

A kinetic analysis of the effects of beta-phenylethylamine on the concentrations of dopamine and its metabolites in the rat striatum.

The purpose of this investigation was to determine whether the increase in the dopamine (DA) concentration in the rat striatum after a rapid iv injection of beta-phenylethylamine (PEA) can be quantitatively explained by the alteration of the striatum PEA concentration using a constructed DA metabolism model and to examine whether the time courses of the striatum DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentration can be described by this DA metabolism model. The time courses of PEA concentration in plasma and the striatum were determined by gas chromatography-mass spectrometry. The plasma PEA concentration was described by a two-compartment model with nonlinear elimination kinetics. The striatum PEA concentration was about 10 times higher than the plasma PEA concentration. The time course of the striatum PEA concentration was described by a diffusion-limited model including a Michaelis-Menten type transport system from plasma to the striatum and nonlinear elimination from the striatum. The DA concentration in the striatum increased immediately after PEA injection. In contrast, the DOPAC concentration in the striatum decreased immediately. HVA concentration in the striatum increased gradually. Assuming that the enhancement of DA concentration in the striatum after PEA injection is caused by the competitive inhibition of PEA on the reuptake of DA into DA neuronal terminals (and the metabolism from DA to DOPAC is then competitively inhibited by PEA in the DA neuronal terminals), the relationship between the enhancement of DA concentration and PEA concentration in the striatum was analyzed using a constructed DA metabolism model. The enhancement of the DA concentration in the striatum was described quantitatively by this model. Thus, it was clarified that a quantitative relationship between PEA concentration and the enhancement of DA concentration in the striatum is present after PEA injection. However, the time courses of the striatum DOPAC (lower dose) and HVA (time delay) concentrations could not be described by this model. These results indicated that other factors might be necessary to explain the time courses of the DOPAC and HVA concentrations in the striatum after PEA injection, such as the separate evaluation of the effect of PEA on the reuptake of DA into DA neuronal terminals and on the monoamine oxidase-B (MAO-B) activity in the DA neuronal terminals, and the metabolic pathway from DOPAC to HVA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Pharmacokinetic and pharmacodynamic studies of centrally acting drugs in rat: effect of pentobarbital and chlorpromazine on electroencephalogram in rat.

Electroencephalogram (EEG) alterations in rat after the i.v. administration of pentobarbital (PTB) and chlorpromazine (CPZ) were measured by power spectral analysis. The time courses of PTB concentrations in plasma, cerebrospinal fluid (CSF) and brain were determined after the i.v. administration of PTB (20, 40 mg/kg) by GC-MS. The PTB concentrations in plasma, CSF and brain could be described by a biexponential equation, a CSF model and a blood flow limited model, respectively. The relationship between the alteration of EEG and the PTB concentrations in the CSF or brain or the effect compartment were analyzed using the sigmoid Emax model. The alteration of EEG after PTB administration could be described by the PTB concentration in these compartments using the sigmoid Emax model. These results indicated that the site of action for the alteration of EEG after PTB administration is in instantaneous equilibrium with the CSF, the brain and the effect compartment. Thus, alterations in EEG after PTB administration can be predicted by monitoring the total PTB concentration in plasma. The alteration of EEG after i.v. administration of CPZ (4 mg/kg) showed a two-phase variation. Although the relationship between the alteration of EEG and the CPZ concentrations in CSF or the striatum or the effect compartment (total and free drug) were analyzed using the linear model, the Emax model or the sigmoid Emax model, the two-phase alteration of EEG after CPZ administration could not be described by any of these models. These results indicated that the pharmacokinetic and pharmacodynamic modeling of CPZ during the alteration of EEG may be complicated due to several pharmacokinetic and pharmacodynamic factors, such as an alteration of the free fraction of CPZ in the striatum, the formation of active metabolites, and two different intrinsic effects of CPZ on the EEG (one in an increase and the other in a decrease of the brain's electrical activity.

Animals↗
PubMed1995

Protein binding of chlorpromazine in vivo and in vitro: effect of chlorpromazine metabolite on chlorpromazine protein binding in rat.

The serum protein binding curve of chlorpromazine (CPZ) on the Scatchard plot in vitro was a two-phase downward curve. However, after i.v. administration of CPZ the curve was altered to an upward curve. To clarify the reasons for these in vivo changes, the influence of chlorpromazine S-oxide (CPZSO), chlorpromazine N-oxide (CPZNO), desmethylchlorpromazine (nor1-CPZ), chlorpromazine sulfone (sul-CPZ) and 7-hydroxychlorpromazine (7-OH-CPZ) on CPZ protein binding were studied in vitro. The results indicated that the characteristics of the CPZ protein binding are altered by the combination of CPZSO or CPZNO or by either of them. Since it was very difficult to explain the relationship between serum total and free concentrations of CPZ in vivo using mass-balance equations like Hill's equation or a competitive inhibition equation on the multiple binding sites for drug, the correlation between the ratio ot total concentration of CPZ metabolites and CPZ (CPZSO/CPZ or CPZNO/CPZ) and the free fraction of CPZ was examined using the in vitro and in vivo data. The correlation between the ratio of CPZSO/CPZ and the free fraction of CPZ was good in both the in vivo and the in vitro studies. There was no statistically significant difference between the population regression coefficient of the two studies. The values of the slope and the intercept became almost the same as those obtained using the in vivo studies when combined with CPZNO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pharmacokinetic analysis of chlorpromazine in rat serum, cerebrospinal fluid and striatum.

The time courses of the total concentration of chlorpromazine (CPZ) and its S-oxide (CPZSO) in serum after i.v. administration of CPZ are described by a two compartment model and a simple metabolism model, respectively. The time course of the free CPZ concentration in serum is predicted by the correlation between the ratio of CPZSO/CPZ and the free fraction of CPZ in serum which was established in the previous study. The time course of CPZ concentration in cerebrospinal fluid (CSF) is described by a basic physiological model in which the CSF compartment is connected with the serum compartment (free drug) by the apparent diffusion clearance. Equilibrium dialysis of the striatum homogenate was carried out to clarify the CPZ disposition in the striatum. Since the binding curves of CPZ in the striatum on the Langmuir plot and the Scatchard plot were a sigmoidal and an upward curve, the time course of the drug's concentration was analyzed on a simple kinetic model designed in conformity with a blood-flow limited model. The time course was described by a simple kinetic model for up to 8 h after CPZ administration. These pharmacokinetic models for CSF and the striatum will be used to analyze the relationship between the pharmacokinetics and pharmacodynamics of CPZ.

Animals↗
PubMed1995

Pharmacokinetic and pharmacodynamic studies of chlorpromazine in rats: effect of chlorpromazine on dopamine and dopamine metabolite concentration in rat striatum.

The concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum were increased after the i.v. administration of chlorpromazine (CPZ). Assuming that the enhancement of dopamine concentration in the striatum after CPZ administration is caused by the release of dopamine from the dopamine neuronal terminals, the relationship between the enhancement of dopamine concentration in the striatum and CPZ concentration in the cerebrospinal fluid (CSF) and the striatum were analyzed using the sigmoid Emax model. The enhancement of dopamine concentration in the striatum could be described quantitatively by this model. The time courses of DOPAC and HVA concentration in the striatum after CPZ administration were analyzed using the dopamine metabolism model, which has an apparent first-order clearance from dopamine to DOPAC and HVA, and also using the Michaelis-Menten type elimination kinetics of DOPAC and HVA. The values of the metabolism parameters for DOPAC and HVA were fixed to the estimated values of the L-dopa study. The calculated values of DOPAC and HVA concentrations in the striatum were greater than those of the observed data. The elimination parameters for DOPAC and HVA were reestimated by the nonlinear least squares method. The time courses of DOPAC and HVA concentration in the striatum could be described using these reestimated elimination parameters. These results indicated that the turnover rate of dopamine and dopamine metabolites, DOPAC and HVA in the striatum after CPZ administration is different from that after L-dopa administration.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Pharmacokinetic and pharmacodynamic studies of L-dopa in rats. I. Pharmacokinetic analysis of L-dopa in rat plasma and striatum.

The purpose of this investigation was to quantitatively describe the pharmacokinetics of exogenous and endogenous L-dopa in plasma and the striatum using a basic physiological model, and to determine the apparent metabolism clearance from L-dopa to dopamine in the striatum. Male Wistar rats were used in this study. The time courses of L-dopa concentrations in plasma and the striatum were determined before and after the rapid i.v. injection of 10, 50 and 100 mg/kg. Plasma and striatum samples were obtained over 480 min (17 time points) from different group of animals and then assayed by HPLC-ECD. The endogenous L-dopa concentration in plasma before drug administration was 2.1 +/- 0.6 mg/l. The exogenous L-dopa concentration declined biexponentially with time after drug injection. The total clearance of exogenous L-dopa in plasma was 3.13(l/h)/kg. The production rate constant of endogenous L-dopa in plasma was 6.59(mg/h)/kg. The value of the production rate constant of endogenous L-dopa in plasma could be calculated by the multiplication of the total clearance of L-dopa and the endogenous L-dopa concentration in plasma before drug injection. The pharmacokinetics of endogenous and exogenous L-dopa in plasma could be described quantitatively by a two compartment model which included the production rate constant of endogenous L-dopa. The time course of L-dopa concentrations in the striatum was analyzed on a hybrid model in which the striatum compartment is independently connected with the plasma compartment by the apparent diffusion clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pharmacokinetic and pharmacodynamic studies of L-dopa in rats. II. Effect of L-dopa on dopamine and dopamine metabolite concentration in rat striatum.

The purpose of this investigation was to quantitatively describe the time courses of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations in the striatum after L-dopa injection using a constructed dopamine metabolism model. The time courses of dopamine, DOPAC and HVA concentration in the striatum of rats was determined before and after the rapid i.v. injection of 10, 50 and 100 mg/kg using the same animals as in the previous report. The endogenous dopamine, DOPAC and HVA concentrations in the striatum before L-dopa administration were 5.9 +/- 0.7 micrograms, 3.6 +/- 0.4 micrograms and 1.0 +/- 0.2 micrograms/g, respectively. The dopamine concentration in the striatum increased immediately after L-dopa injection, with the peak concentration (15.9 +/- 0.5 micrograms/g) occurring at 3 min; then it returned to the pre-medication level until 2 h at 100 mg/kg dosing. The time course of dopamine concentration in the striatum was analyzed on a constructed dopamine metabolism model which has a zero-order production rate for the production of dopamine (i.e. release from the dopamine neuronal terminals) and two apparent first-order clearance terms, one from L-dopa to dopamine, which was estimated in the previous report, and the other from dopamine to dopamine metabolites (DOPAC and HVA). However, the time course of dopamine concentration in the striatum could not be described by this model.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Microbial contamination of enteral feeding solution and its prevention.

In an investigation of microbial contamination of enteral feeding solutions, all 22 residual solutions obtained immediately after administration were contaminated at concentrations of 10(3) to 10(6) viable counts/ml. Major contaminants were glucose-nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus var anitratus. Contamination seemed to have been caused by frequent reuse of bag-type containers and the infusion tubes connected to the bags, neither of which can be washed or dried. Decontamination methods were evaluated by using polypropylene containers that can be washed and disinfected for administration. Few Serratia marcescens on the inside wall of the container were removed by rinsing with tap water, alone or in combination with detergent scrub. Tap water and detergent plus air-drying at 56 degrees C for 1 hour reduced Serratia marcescens only somewhat. Tap water and detergent plus immersion in 0.01% sodium hypochlorite for 1 hour or in water at 70 degrees C for 3 minutes eliminated all 10(11) cells of Serratia marcescens.

Bacteria↗
PubMed1992

Microbial contamination of enteral feeding solution and its prevention.

In an investigation of microbial contamination of enteral feeding solutions, all 22 residual solutions obtained immediately after administration were contaminated at concentrations of 10(3) to 10(6) viable counts/ml. Major contaminants were glucose-nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus var anitratus. Contamination seemed to have been caused by frequent reuse of bag-type containers and the infusion tubes connected to the bags, neither of which can be washed or dried. Decontamination methods were evaluated by using polypropylene containers that can be washed and disinfected for administration. Few Serratia marcescens on the inside wall of the container were removed by rinsing with tap water, alone or in combination with detergent scrub. Tap water and detergent plus air-drying at 56 degrees C for 1 hour reduced Serratia marcescens only somewhat. Tap water and detergent plus immersion in 0.01% sodium hypochlorite for 1 hour or in water at 70 degrees C for 3 minutes eliminated all 10(11) cells of Serratia marcescens.

Colony Count, Microbial↗
PubMed1992

Microbial contamination of ambient air by ultrasonic humidifier and preventive measures.

The microbially contaminated ultrasonic humidifier (UH) causes humidifier fever. The number of airborne viable bacteria was determined when the UH was operating, and other methods to humidify the air of hospital wards were also examined. A UH contaminated with 10(5) bacteria ml(-1), a level common in hospitals, increased the bacterial count in the air from 860 m(-3) to 88,000 m(-3) at a distance of 3 m from the humidifier. Thus UH in hospitals may contaminate the air and be a potential hazard to patients. Contamination was slight when a washable and disinfectable ultrasonic nebulizer was used with disinfection at 24 h intervals. In tracheostomy patients requiring a high degree of air humidification, ultrasonic nebulizers which are readily washed and disinfected are recommended.

Aerosols↗
PubMed1991

Analysis of K. pneumoniae by monoclonal antibody: immunohistochemical detection of K. pneumoniae surface antigen injected into mice and rats.

The monoclonal antibody Kp62 recognized surface antigenic determinants of some strains of Klebsiella pneumoniae. The antigen recognized by Kp62 was demonstrated on the bacterial surface using immunoelectron microscopy. Kp62 reacted with K. pneumoniae No. 1 or K. pneumoniae B 5055 and lipopolysaccharide (LPS) from the same bacteria. However, Kp62 was not inhibited by the LPS from Escherichia coli (E. coli) O111:B4 and E. coli O55:B5. Thus, Kp62 might be a useful monoclonal antibody to detect K. pneumoniae and LPS from K. pneumoniae. The possibility to visualize the localization of K. pneumoniae LPS injected into animals using immunohistochemical methods with this monoclonal antibody was examined. It was possible to detect the injected LPS in the spleen of mouse and rat with the monoclonal antibody to K. pneumoniae. In order to detect the early events taking place in the spleen after intravenous injection of LPS, time course of LPS distribution in mice and rats was studied. After 30 min, 2, 4, 8 and 24 h LPS localized in the marginal zone (MZ) in mice and rats, although the degree of LPS positive cells varied. The cells responsible for trapping the injected LPS appeared to be marginal zone macrophages. The early trapping of LPS by marginal zone macrophages was thought to be important for the following immune responses to the injected LPS. Interestingly the antigenic determinant on the injected LPS appeared to last long on or within the cells in the spleen from the injected animals. Such a remaining antigen might be important for the continuous stimulation of B cells by the LPS. With respect to the distribution of red pulp (RP) and white pulp (WP), we found the varied distribution of LPS between mouse and rat, and SPF and conventionally fed (Conv) animals. For example, LPS-positive cells in RP of rat were scarce, while significant degree of LPS-positive cells were observed in mice. And in WP, LPS-positive cells were observed in Conv DA rats, but not in mice or SPF-fed Wistar rats. These results may suggest that the mode of antigen processing may be different in the spleen of rat and mouse or even among the different strain of rats and previous sensitization to the LPS (or the similar antigenic determinants) may lead to the different distribution of LPS in the spleen. The monoclonal antibody specifically raised against K. pneumoniae was shown to be very useful to follow the fate of LPS derived from K. pneumoniae using immunohistochemical method.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Development of the convenient and direct numerical analytical method of the pharmacokinetics of phenytoin by an ordinary and/or the Bayesian weighted least-squares method using the program MULTI2(BAYES).

A Simple and convenient numerical integration method was developed for the purpose of analyzing the pharmacokinetics of phenytoin not only at steady state but also at non-steady state. The algorithm was linked on a nonlinear least-squares method program MULTI2(BAYES). The computing time was significantly decreased compared to Runge-Kutta-Gill Method at analysis by the Simplex algorithm and calculating precision was higher, especially at a large integration interval. This method was found to be sufficiently applicable to the analyses of the serum concentrations of phenytoin at non-steady state as well as at steady state and the dosage adjustment by simulation. The flexibility of analyzed parameters on a microcomputer can be overcome by analyzing at the integration subinterval smaller than 0.25 h with the appropriate initial values of parameters, although very time consuming, or by using the Bayesian method with appropriate population parameters.

Bayes Theorem↗
PubMed1988

Production of monoclonal antibodies against surface antigenic determinants of Klebsiella pneumoniae.

The production of four murine monoclonal antibodies (Kp26, Kp53, Kp62 and Kp71) to Klebsiella pneumoniae surface antigen(s) is described. The binding of all four monoclonal antibodies to K. pneumoniae was inhibited by F(ab')2 fragments of normal human serum IgG, suggesting that the antigenic determinants of K. pneumoniae detected by the four monoclonal antibodies may be similar to those recognized by human serum IgG. The antigen identified by Kp62 was purified from a deoxycholate-solubilized bacterial fraction using immunoaffinity chromatography. The molecular weight of the antigen was determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis to be 50,000-70,000.

Animals↗
PubMed1987

Intoxication with sulindac, tiaramide hydrochloride and diclofenac sodium.

Overdosage intoxication of sulindac, tiaramide and diclofenac caused excitability of central nervous system, followed by unconsciousness. The case was treated with ordinary therapies and direct hemoperfusion (DHP). Serum concentrations of these drugs and their metabolites were correlated well with the clinical symptoms. DHP may be effective to eliminate these drugs and their metabolites.

Adult↗
PubMed1987

The metabolism of trichloroethylene and its metabolites in the perfused liver.

The metabolism of trichloroethylene (TRI) and its metabolites, chloral hydrate (CH), trichloroethanol (free-TCE) and trichloroacetic acid (TCA), were examined in the isolated perfused rat liver, to clarify the role of the liver in the metabolism of TRI. TRI was rapidly converted to TCE and TCA by the perfused liver. TCA was produced from TRI about 2.5 times greater than was total-TCE. CH was metabolized to TCE and TCA immediately. TCA was also a dominant metabolite of CH over total-TCE. TCE(free type) was speedily conjugated by the liver. A portion of TCE was converted to TCA. Less than 10% of these metabolites produced by the liver were excreted into the bile. Most of them appeared in the perfusate.

Animals↗