Biomedical subjects

O Nagata

Publications and source records attributed to O Nagata.

At least 55 records · Page 3Linked to original sources

PubMed1997

Decalcification of calcium polycarbophil in rats.

The in vivo decalcification of calcium polycarbophil was examined. The decalcification ratio of [45Ca]calcium polycarbophil in the stomach after oral dosing to rats was more than 70% at each designated time and quite closely followed in the in vitro decalcification curve, indicating that the greater part of the calcium ion is released from calcium polycarbophil under normal gastric acidic conditions. The residual radioactivity in rat gastrointestine was nearly equal to that after oral administration of either [45Ca]calcium chloride + polycarbophil. The serum level of radioactivity was nearly equal to that after oral dosing of [45Ca]calcium lactate. These results indicate that the greater part of orally administered calcium polycarbophil released calcium ions to produce polycarbophil in vivo.

Acrylic Resins↗

PubMed1997

[Examples of pitfalls in statistical analysis--5: Analysis of a multiple factor model].

When we analyze the effects of multiple factors, it is inadequate to repeat simple comparisons of the groups divided by a factor. The reasons for this are twofold, i.e., the total error rate of the study grows higher in proportion to the number of comparisons, and we cannot evaluate the relationships between the factors. It is reasonable in such a situation to use multivariate analyses which are developed to analyze multiple factor models, by changing the analytic point of view. In this article, I present an example to illustrate several types of mistakes which occur when we simply compare the two groups divided by one factor for other multiple factors, and explain the evaluation with correlation analysis and factor analysis.

Adult↗

PubMed1997

[Examples of pitfalls in statistical analysis--6. Evaluation of data consisting of the elapsed time between two events].

In comparing two or more groups, we usually compare the values of averages and/or medians of the groups. We do this because the averages can be easily calculated from the raw data, and because we feel able, to some extent, to recognize the results from the values. However, since the comparison with the averages is only an evaluation of one aspect of the data, we have to keep in mind the risk of unreasonable analysis and erroneous results. Particularly in evaluating data consisting of the elapsed time between two events of interest, survival analysis is a suite of statistical analyses. In this article, I will show an example to illustrate the method used to compare the elapsed time between two groups using survival analysis.

Adult↗

PubMed1996

Sensitive analytical method for the novel H1-receptor antagonist HSR-609 in human plasma and urine by high-performance liquid chromatography with pre-column fluorescent derivatization.

A simple and sensitive method for quantitation of HSR-609 (I) in human plasma and urine was developed using HPLC with the fluorescence labelling reagent 4-(N,N-dimethylaminosulfonyl)-7-N-piperazino-2,1,3-benzox adi azole (DBD-PZ). Compound I was extracted from human plasma and urine, and derivatized by reaction with DBD-PZ in the presence of Mukaiyama reagent A, an equimolar solution of 2,2'-dipyridyl disulfide (DPDS) and triphenylphosphine (TPP) in acetonitrile. The reaction mixture was cleaned up by liquid liquid extraction following the derivatization. The conjugate was analyzed by ion-pair-HPLC with fluorometric detection. The quantitation limits for I were 0.5 ng/ml in plasma and 5 ng/ml in urine. Using this method, plasma concentration and urinary excretion of I were studied after oral administration of I to human volunteers.

Benzoxepins↗

PubMed1996

Physicochemical properties of calcium polycarbophil, a water-absorbing polymer.

The physicochemical properties of calcium polycarbophil were examined. Calcium polycarbophil was decalcified rapidly under acidic conditions, affording polycarbophil. Polycarbophil absorbed about 10 times its own weight of water under acidic conditions, but the swelling ratio markedly increased at above pH 4.0 and reached 70 times the initial weight under neutral conditions. The swelling of polycarbophil was not affected by non-ionic osmolarity, but was affected by ionic strength, showing a decrease with increase of ionic strength. Monovalent metal ions such as sodium and potassium ions in gastrointestinal fluid did not reduce the equilibrium swelling of polycarbophil, but divalent ions such as calcium and magnesium ions did. However, calcium ion only slightly reduced the equilibrium swelling under sodium-rich conditions. The viscosity (as an indicator of fluidity) of polycarbophil was larger than that of CMC-Na at every shear rate and polymer content examined.

Acrylic Resins↗

PubMed1996

Effect of polycarbophil on the absorption of nutrients.

The effects of polycarbophil on the absorption of various nutrients were evaluated by several in situ methods. Polycarbophil reduced the absorption of 3-O-methyl-D-glucose (3-OMG) and L-phenylalanine in the in situ loop and the in situ perfusion methods, but it did not affect the absorption of these nutrients in an open system, the in situ modified loop method, which is closer to physiological conditions. It also did not affect the absorption of vitamin A or phosphatidylcholine-L-alpha-dipalmitoyl in the latter system. These results indicate that the absorption of nutrients is probably not altered by polycarbophil under physiological conditions.

3-O-Methylglucose↗

PubMed1996

[Examples of pitfalls in statistical analysis--1. Summarizing your data before statistical analysis].

When conducting studies, it is important to summarize the gathered data before beginning calculations for statistical analysis. If the methods used to summarize the data are inadequate for purposes of the analysis you want to perform, many misleading or unreasonable discussions that are normally avoidable arise. If there is any uncertainty in the way data are handled, for example, confusion as to whether comparison of mean (parametric analysis) or comparison of median (nonparametric analysis) is used, or whether the data are paired or unpaired, it is impossible to make good charts that show us the features of the data at a glance. In this article, I will address several frequently asked questions about summarizing data, and discuss making suitable charts by presenting a typical example.

Data Collection↗

PubMed1996

[Examples of pitfalls in statistical analysis--2. Parametric and nonparametric analyses].

When conducting statistical analysis, it is essential to use parametric and nonparametric analyses which properly accord with the attributions of data. What is often overlooked, however, is the need to select the most suitable method of spatistical analysis for the model of the studies. Parametric analysis certainly cannot be relied upon in all situations to yield the best resolutions, and even if we strictly distinguish between the use of parametric and that of nonparametric analyses, we still have done nothing to improve the resolutions themselves. In this article, I discuss several frequently asked questions by presenting an example in which I use parametric analysis on data that should be analyzed by nonparametric analysis.

Drug-Related Side Effects and Adverse Reactions↗

PubMed1996

[Examples of pitfalls in statistical analysis--3: Why do we need to use multiple comparison procedures?].

When comparing the means of more than three groups, we first have to carry out an analysis of variance (ANOVA) to confirm whether all of the means of each group are equal, and we then have to evaluate all possible pairwise comparisons with multiple comparison procedures. If we use only the unpaired t-test for all pairwise comparisons without ANOVA and multiple comparison procedures, we are more likely not only to erroneously conclude that two means in a pair are significantly different when actually they are not, but also to create a contradiction between pairs of means with large differences which are not considered significant, and pairs of means with small differences which are considered significant. In this article, I discuss two problems in comparing the means of multiple groups by presenting an example in which I apply unpaired t-test on data that should be analyzed by ANOVA and multiple comparison procedures.

Analysis of Variance↗

PubMed1996

[Examples of pitfalls in statistical analysis--4: What is a type II error?].

When assessing the results of statistical analysis, we have to consider two types of errors, i.e., type I errors, which present the risk of erroneously judging a true hypothesis to be false, and type II errors, which present the risk of erroneously judging a true hypothesis to be true. If we use only type I errors to detect the significances in statistical analysis, we can not avoid making the erroneous judgement that a true hypothesis is false. When the results of analysis are not significant, we have to calculate type II errors and discuss the probabilities of having missed the truth. In this article, I present an example to illustrate two types of errors which can occur in assessing the result of statistical analysis.

Anesthesia, Inhalation↗

PubMed1995

Glutamate N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists administered into the brain stem depress the renal sympathetic reflex discharges evoked by single shock of somatic afferents in anesthetized rats.

The involvement of glutamate receptors in the central transmission of somatosympathetic reflexes was studied by examining, in anesthetized rats, the effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, and CNQX, a non-NMDA receptor antagonist, on two reflex components, the A- and C-reflexes evoked in the left sympathetic renal nerve by a single shock to the left tibial nerve. The A-reflex elicited by myelinated A fiber stimulation and the C-reflex elicited by unmyelinated C fiber stimulation were depressed, in a dose-dependent manner, following administration of either MK-801 or CNQX into the cisterna magna (i.c.m.). Intrathecal (i.t.) administration of MK-801 did not have any effect on either A- or C-reflexes, while i.t. administration of CNQX had a slight effect on the A-reflex (significantly on the A-reflex only when treated with the highest dose of 100 ng) and the C-reflex. These results indicate that both NMDA and non-NMDA receptors, stimulated by glutamate released possibly as a neurotransmitter, are involved in the central transmission pathways of somatosympathetic reflexes at the level of the brain stem, but not the spinal cord.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1994

Analysis of urinary and biliary metabolites of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid in rats by liquid chromatography-frit-fast atom bombardment mass spectrometry.

The urinary and biliary metabolites of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid [(+)-MPPB] were examined in rapid-metabolizing (RM) and slow-metabolizing (SM) male Sprague-Dawley rats by means of liquid chromatography-frit-fast atom bombardment mass spectrometry. In the RM-phenotyped rats, unchanged (+)-MPPB could not be detected in urine or bile, but 4-carboxyphenyl-MPPB was detected in bile. In the SM-phenotyped rats, unchanged (+)-MPPB was detected in bile and unchanged (+)-MPPB and beta-oxidized MPPB in urine. Thus, the inter-individual difference in (+)-MPPB metabolism in rats was confirmed in vivo.

Animals↗

PubMed1994

Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures.

The transport mechanism of the H1-antagonist mepyramine at the blood-brain barrier (BBB) was studied by using primary cultured monolayers of bovine brain capillary endothelial cells (BCEC). The initial uptake of [3H]mepyramine into the BCEC showed strong temperature and concentration dependency, indicating that it involves both saturable and nonsaturable processes. Transport at the luminal membrane may be the rate-limiting process in the transcellular transport, since the values of the uptake coefficient of [3H]mepyramine at the luminal membrane (609 microliters/mg protein/min) and the transcellular permeability coefficient (488 microliters/mg protein/min) are very similar. The initial uptake of [3H]mepyramine was not affected by metabolic inhibitors, but was stimulated by preloading with the drug. Mepyramine appears to be transported into the BCEC by a carrier-mediated transport system which does not require metabolic energy, probably via a facilitated diffusion mechanism.

Animals↗

PubMed1994

Carrier-mediated transport of H1-antagonist at the blood-brain barrier: a common transport system of H1-antagonists and lipophilic basic drugs.

The blood-brain barrier (BBB) transport system for H1-antagonists was studied using primary cultured bovine brain capillary endothelial cells (BCEC). The uptake of [3H]mepyramine was inhibited by various H1-antagonists. Ketotifen competitively inhibited [3H]mepyramine uptake with an inhibition constant (Ki) of 46.8 microM. Lipophilic basic drugs such as propranolol, lidocaine and imipramine significantly inhibited [3H]mepyramine uptake. In particular, propranolol inhibited [3H]mepyramine uptake competitively at an inhibition constant (Ki) of 51.1 microM. Moreover, in ATP-depleted BCEC, [3H]mepyramine uptake was stimulated by preloading with H1-antagonists and lipophilic basic drugs. These results indicated that H1-antagonists are transported across the BBB via a carrier-mediated transport system common to lipophilic basic drugs.

Animals↗

PubMed1994

Transport mechanism of an H1-antagonist at the blood-brain barrier: transport mechanism of mepyramine using the carotid injection technique.

The blood-brain barrier (BBB) permeability of mepyramine was measured by the carotid injection technique to elucidate the transport mechanism of an H1-antagonist in the central nervous system. Mepyramine was found to enter the brain by saturable and carrier-mediated transport. The in vivo kinetic parameters were estimated as follows: the maximum uptake rate (Jmax) was 7.12 +/- 1.37 mumol/min/g of brain, the Michaelis constant (Kt) was 4.40 +/- 2.00 mM, and the nonsaturable first order rate (Kd) was 0.28 +/- 0.02 ml/min/g of brain. The mepyramine transport was not inhibited either by nutrients or by choline, hemicholinium-3, though it was inhibited by the classical H1-antagonists such as diphenhydramine, diphenylpyraline, and also by propranolol. The above inhibitory effects suggest that a transport system different from the amine transport system exists for the BBB transport of mepyramine, and that this transporter is common not only for H1-antagonists but also for basic drugs.

Animals↗

PubMed1994

Characterization of acetylcholinesterase-inhibition by itopride.

Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.

Acetylcholine↗

PubMed1993

Aspergillus nidulans nuclear proteins bind to a CCAAT element and the adjacent upstream sequence in the promoter region of the starch-inducible Taka-amylase A gene.

Aspergillus nidulans was used as an intermediate host to investigate the regulation of the Taka-amylase A (TAA) gene from Aspergillus oryzae. The induction of Taa by starch was confirmed to be regulated at the transcriptional level by analyzing the transcripts specific for Taa synthesized in vitro in nuclei from starch- and glucose-grown cells. A 55 bp DNA fragment containing a consensus CCAAT sequence from the promoter region of the Taa gene was shown to confer starch inducibility on the gene. A nuclear extract from starch-grown cells was assayed for proteins which bind to the promoter region of the Taa gene. A protein designated AnCP1 bound to the CCAAT sequence. A nuclear extract from glucose-grown cells contained two DNA-binding proteins designated AnCP2 and AnNP1. AnCP2 bound to the same CCAAT sequence as AnCP1, while AnNP1 bound to the 25 bp region just upstream of the AnCP2 binding site. Occupancy of the two binding sites appeared to be mutually exclusive, which is suggestive of a negative regulatory mechanism for gene expression.

Aspergillus nidulans↗

PubMed1993

Inter-individual differences of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid ((+)-MPPB) disposition in rats.

Inter-individual differences of drug plasma concentration were recognized in male Sprague-Dawley (SD) rats after a p.o. or i.v. administration of (+)-MPPB. Rats could be divided into two phenotypes, the rapid-metabolizing group (RM) and the slow-metabolizing group (SM). The hepatic clearance (CLliver) of RM was about 10 times larger than that of SM. Outbred SD(male, female), and Wistar(male) rats were mixtures of RM and SM. On the other hand, all inbred Lewis(male) rats were RM, and all inbred F344(male) and ACl(male) rats were SM.

Animals↗