Biomedical subjects

Kenjiro Koga

Publications and source records attributed to Kenjiro Koga.

7 recordsLinked to original sources

PubMed2006

Cytotoxic evaluation of cubic boron nitride in human origin cultured cells.

The aim of this study was to evaluate the cytotoxicity of cubic boron nitride (cBN), a component of surgical cutting tools. The small quantities of cBN that typically remain on implants as a result of the manufacturing process may act as abrasives, injuring tissues surrounding the implant. To determine how cBN affects cells, we treated human neuroblastoma cells (NB-1) and human articular chondrocytes (nHAC-kn) with different concentrations of cBN powder and assessed cell growth and cell survival using the methyl-thiazol-tetrazolium (MTT) assay and a fluorescence probe assay. We also assessed the effects of tungsten carbide (WC) and cobalt (Co), two common components of joint implants, on cell growth and cell survival. Both cBN and WC moderately inhibited NB-1 and nHAC-kn cell growth. However, cBN and WC did not affect cell survival, even at high concentrations (40 microg/ml). By contrast, Co affected cell survival, inducing cell death in both cell types at increasing concentrations. These results suggest that cBN may be less toxic than WC alloys containing Co.

3T3 Cells↗

PubMed2006

Enhancing mechanism of Labrasol on intestinal membrane permeability of the hydrophilic drug gentamicin sulfate.

The aim of this study was to clarify the mechanism by which caprylocaproyl macrogol-8 glyceride (Labrasol) enhances the intestinal absorption of gentamicin sulfate (GM), a drug that has poor permeability but relatively high solubility. We studied the following characteristics: (i) the phase behavior of Labrasol in aqueous solution, (ii) the affinity of GM to Labrasol micelles, and (iii) the interaction between Labrasol and membrane lipids. We measured the critical micelle concentration of Labrasol in aqueous solution to be approximately 0.01%. The average diameters of Labrasol micelles in 2% and 25% solutions were approximately 10 nm and 20 nm, respectively, indicating that micelles increase in size with increasing Labrasol concentration. Although GM dissolved in 5% Labrasol solution was dialyzable, GM dissolved in either 25% or 50% Labrasol solutions was not, suggesting that GM exists in the hydrophilic region of the Labrasol micelle or in the high affinity region of the micelle surface where GM is retained. In membrane permeability experiments and electrophysiological studies conducted with rat ileum, only 25% Labrasol solution enhanced GM permeability, but did not remarkably affect membrane resistance. Furthermore, Labrasol increased membrane lipid fluidity as determined by fluorescence anisotropy in porcine intestinal brush border membrane liposomes. These results suggest that high concentrations of Labrasol solution enhance membrane permeability of GM via a transcellular rather than a paracellular route. We propose the following mechanism: Labrasol micelles grow when the concentration of Labrasol exceeds 20%, at which point GM shows high affinity for the hydrophilic region of the micelles. Since Labrasol micelles increase membrane lipid fluidity, the membrane permeability of GM is concomitantly enhanced.

Absorption↗

PubMed2004

Membrane permeability and antipyrine absorption in a rat model of ischemic colitis.

The aim of this study was to determine whether the duration of ischemia affects antipyrine absorption in the large intestine. This was carried out in a rat model of ischemic colitis in which ischemia and associated inflammation was induced by marginal vessel ligation. Blood flow was disrupted by positioning an o-ring around the distal rectum and ligating the marginal vessel at two locations in the hind-gut ligament artery region. Ligation was performed for 1, 2, 3, and 5h. We assessed large intestine damage by measuring key indicators of inflammation, myeloperoxidase (MPO) activity and thiobarbituric acid reactant substrates (TBARS) in the mucosa and by histological staining with hematoxylin-eosin stain. Antipyrine membrane permeability was assessed in Ussing-type diffusion chambers, and related pharmacokinetics were calculated from antipyrine plasma concentration measurements following colon administration of the drug. Vessel ligation caused some sloughing of epithelial cells and elevated the MPO and TBARS levels. Prolonged ligation failed to affect the apparent permeability coefficient (P(app)) of antipyrine. Prolonged ligation, however, gradually increased plasma antipyrine concentrations to near control levels. This increase was paralleled by increases in the absorption rate constant AUC and antipyrine bioavailability. Taken together, these results suggest that the absorption kinetics of antipyrine may depend on blood flow changes in the large intestine that occur with inflammation.

Animals↗

PubMed2004

Clove oil prevents glycyrrhizin gel formation in aqueous solution.

One persistent problem with using therapeutic concentrations of glycyrrhizin (GZ) is that, at these high concentrations, it forms a gel in an aqueous solution. We previously solved this problem by dissolving GZ in a highly concentrated phosphate buffer. Unfortunately, the resulting GZ solution has a hyperosmotic pressure that renders it unsuitable for use in patients. The aim of this study was to prepare a highly concentrated GZ solution having an osmotic pressure ratio of 1 and a pH of 7.4. By adding small amounts of oil and using a 100 mM phosphate buffer, we achieved an emulsified GZ solution that is stable at room temperature and has a physiological osmotic pressure and pH. When clove oil was used as an emulsifier, the gel formation temperature of GZ solution decreased appreciably compared to that of GZ solution without clove oil. Using scanning electron microscopy (SEM), we examined the detailed characteristics of GZ gels prepared from solutions with or without clove oil. SEM of cross sections of GZ gels revealed an irregular structure in gels prepared with clove oil, indicating that clove oil prevented the formation of the intermolecular GZ networks typically characterized by gels derived from pure GZ solutions.

Chromatography, High Pressure Liquid↗

PubMed2003

Preparation and rectal absorption of highly concentrated glycyrrhizin solution.

We developed a simple method for preparing a highly concentrated solution of glycyrrhizin monoammonium salt (GZ) at low viscosity with no surfactants nor organic solvents and investigated the absorption profile after rectal administration to rats. GZ (200 mg/ml) was dissolved in phosphate buffered solution, pH 7.0; over 350 mM concentration was maintained for the aqueous solution without gel-formation. When glycerin was used as a non-aqueous formulation, GZ did not form gel. Apparent permeability coefficients of GZ obtained from 350 mM phosphate buffered solution (pH 7.0) and glycerin solution through rat rectal mucosa estimated by in vitro parallel diffusion chamber technique were 0.686 x 10(-6) and 0.379 x 10(-6) cm/s, respectively. On the other hand, the area under plasma concentration-time curves of GZ in 400 mM phosphate buffer (pH 7.0) and glycerin formulations after rectal administration to the rat were significantly higher than that in polyethylene glycol 400/propylene glycol (55 : 5) formulation. Maximum plasma concentrations of these formulations were dependent on the apparent permeability coefficients of GZ. Increased absorption observed by phosphate buffered formulation accompanied no pronounced histological damage in mucosa. These results demonstrate that addition of a highly concentrated phosphate salts is effective not only for lowering the viscosity of a highly concentration of GZ solution, but also for improving the mucosal GZ absorption.

Administration, Rectal↗

PubMed2002

In vitro and in situ evidence for the contribution of Labrasol and Gelucire 44/14 on transport of cephalexin and cefoperazone by rat intestine.

In vitro and in situ intestinal transport of beta-lactam antibiotics in the presence of two novel pharmaceutical excipients, caprylocaproyl and lauroyl macrogolglycerides (Labrasol and Gelucire 44/14), is described. The objective was to compare the effects of both macrogolglycerides on the intestinal transport of cephalexin, a substrate of oligopeptide transporters, and cefoperazone, a non-substrate of them. The in vitro transport studies were performed using a sheet of rat jejunum mounted in Ussing-type diffusion chambers. The in situ studies used an isolated internal loop model in the rat. Labrasol and Gelucire 44/14 were used as the excipients at low concentrations (0.01-0.5%, w/v). The membrane permeability of both drugs was compared by apparent permeability coefficients (P(app)) determined from changes in the amount of permeation vs. time in in vitro studies and by apparent absorptive clearance (CL(app)) determined from changes in the steady state drug concentration of perfusate in in situ studies. The P(app) value of cephalexin increased with an increase in the concentration of Labrasol (0.05-0.5%) compared to the value without Labrasol. The enhancing effect of Labrasol on cephalexin transport was similarly observed in in situ studies, and when 0.5% Labrasol was used in the presence of glycyl-L-leucine or L-alanyl-L-alanine, 60 or 46% enhancement of the active transport of cephalexin by Labrasol was obtained. On the other hand, Gelucire 44/14 did not affect the P(app) and CL(app) of either drug. The different effects of the excipients on cephalexin transport were thought to be due to the influences of size parameters such as a polydispersity index and particle size, and the change in the short-circuit current of jejunum by the addition of the excipient.

Animals↗

PubMed2002

A simple method for the selection of a suitable emulsifier based on color difference.

The purpose of this study was to establish a simple and rapid method for selecting a nonionic surfactant to prepare an emulsion that can maintain a stable emulsification phase. As an index of the degree of emulsification, the white chromaticity of the prepared sample was measured using a color difference meter. When liquid paraffin was used as an oil, the color difference (dE(H)) was shown as a change in a V-shaped curve depending on changes in the hydrophile-lipophile balance (HLB) number of sorbitan ester, polyoxyethylene sorbitan ester, or polyethyleneglycol ester. Although there was a difference in the minimal value of dE(H) in these experiments, the dE(H) was similar to the required HLB of liquid paraffin (HLB=10). On the other hand, no relationship was found between the HLB number and color difference when polyglycerol ester was used. It seems that there was possibility of the effect by the lowering of apparent HLB with a collapse of the hydration. These results indicate that color difference could be utilized for the selection of surfactants, except for polyglycerol ester.

Colorimetry↗