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Biomedical subjects

Y Katagiri

Publications and source records attributed to Y Katagiri.

At least 19 recordsLinked to original sources
PubMed1992

Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats.

The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats. At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat. Sparfloxacin concentrations were assayed by HPLC. Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen. Binding sparfloxacin to serum protein slightly decreased after the coadministration. No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points. The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier. These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.

Algorithms↗
PubMed1992

Effect of fenbufen on the entry of new quinolones, norfloxacin and ofloxacin, into the central nervous system in rats.

The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin, into the central nervous system (CNS) of rats, and the effect of fenbufen on this was investigated. At various times after the administration of a bolus intravenous dose of norfloxacin or ofloxacin (10 mg kg-1) with or without fenbufen (20 mg kg-1), serum and cerebrospinal fluid (CSF) samples and whole brain were collected from the rats and the concentration of norfloxacin or ofloxacin in each sample was determined. Serum concentrations of both quinolones declined biexponentially with time and were significantly elevated by coadministration with fenbufen at the terminal phase. The fractions of these quinolones bound to serum protein were not altered by coadministration with fenbufen. Coadministered fenbufen raised the brain concentrations of both quinolones but did not affect their brain to serum unbound concentration ratios. In contrast, CSF to serum unbound concentration ratios as well as CSF concentrations of norfloxacin and ofloxacin were elevated by coadministration with fenbufen. Apparent diffusional clearances between blood and CSF of norfloxacin and ofloxacin estimated by the physiological model analysis increased by 1.9 and 2.6 times, respectively, after coadministration with fenbufen. These findings suggest that coadministered fenbufen may facilitate the entry of norfloxacin and ofloxacin into the CNS.

Animals↗
PubMed1992

Salivary excretion of mexiletine after bolus intravenous administration in rats.

Salivary excretion of mexiletine was investigated following bolus intravenous administration (10 mg kg-1) in rats. Parotid and mandibular saliva was collected separately by stimulating salivation with constant rate infusion of pilocarpine (3 mg kg-1 h-1). The mexiletine levels in blood plasma and parotid and mandibular saliva declined biexponentially with time in almost parallel fashion. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva. Significant correlations were observed when all data relating mexiletine concentration in plasma and saliva were included (P less than 0.001). The saliva/plasma drug concentration ratios (S/P ratios) did not vary to a large extent (0.56 +/- 0.10 for parotid saliva, 0.21 +/- 0.06 for mandibular saliva), but there was a consistent tendency for the higher plasma drug levels in the distribution phase to produce relatively high S/P ratios for both parotid and mandibular saliva. Moreover, the plasma mexiletine levels calculated by the equation of Matin et al (1974) employing the observed values for the saliva drug level, saliva pH and free fraction of mexiletine in plasma were significantly higher than the observed drug levels. Therefore, it is suggested that the salivary excretion of mexiletine could not be explained quantitatively by simple, passive secretion based on pH-partition theory.

Animals↗
PubMed1992

Pharmacokinetics of [6]-gingerol after intravenous administration in rats with acute renal or hepatic failure.

The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal failure induced by bilateral nephrectomy, or those with acute hepatic failure induced by a single oral administration of carbon tetrachloride (CCl4), to clarify the contribution of the kidney and liver to the elimination process of [6]-gingerol. After bolus intravenous administration, a plasma concentration-time curve of [6]-gingerol was illustrated by a two-compartment open model. There was no significant difference in either the plasma concentration-time curve or any pharmacokinetic parameters between the control and nephrectomized rats. It is suggested, therefore, that renal excretion does not contribute at all to the disappearance of [6]-gingerol from plasma in rats. In contrast, hepatic intoxication with CCl4 elevated the plasma concentration of [6]-gingerol at the terminal phase. Its elimination half-life increased significantly, from 8.5 to 11.0 min, in CCl4-intoxicated rats. The extent of [6]-gingerol bound to serum protein was more than 90% and was affected very slightly by the CCl4-intoxication. These aspects indicate that [6]-gingerol is eliminated partly by the liver.

Acute Disease↗
PubMed1992

Interaction of platelets and blood vessels--vascular injuries induced by platelet activation in vivo.

We have found that vascular injuries are induced by intravascular aggregation of platelets activated by arachidonic acid (AA) or ADP. The characteristic findings are the appearance of vacuoles in endothelial cells and eventual deendothelialization. In deendothelialized regions, formation of platelet thrombi was observed. The platelets in the thrombi were stained with 2T60, a monoclonal antibody that recognizes activated platelets. The change was more remarkable in the AA-injected animals because AA has a stronger platelet activating effect and a detergent effect on the endothelium. The ADP-injection experiments clarified the role of platelets in vascular injury. These findings suggest that activated platelets play a role in the genesis of vascular injuries, and that their role is related to thrombus formation.

Adenosine Diphosphate↗
PubMed1992

[Detection of circulating activated platelets by anti-GMP-140 monoclonal antibodies].

The clinical significance and detection methods for circulating activated platelets are reviewed. It has been recently demonstrated that three kinds of platelet granules, dense granule, alpha-granule and lysosome, have specific membrane proteins; granulophysin, GMP-140 (PADGEM) and CD63 antigen, respectively, and that these specific granule-membrane proteins become exposed on the surface of the activated platelets. It is believed that detection of circulating activated platelets, using monoclonal antibodies specific to these granule-membrane, may be reliable and diagnostic value in thrombotic and prethrombotic diseases. Preliminary clinical studies using 2T60, a newly developed anti-GMP-140 monoclonal antibody, was presented.

Antibodies, Monoclonal↗
PubMed1991

Enhancement by IL-1 beta and IFN-gamma of platelet activation: adhesion to leukocytes via GMP-140/PADGEM protein (CD62).

We have examined the effect of inflammatory cytokines on the platelet activation. IL-1 beta and IFN-gamma were found to enhance the adhesion of thrombin-treated platelets to monocytic leukemia cells (U937), when the adhesion was assayed by platelet-mediated cell agglutination. The agglutination was inhibited by a monoclonal anti-GMP140 antibody or EDTA, suggesting that the enhanced platelet adhesion to the leukemic cells was mediated by GMP140. In addition, these cytokines also increased the release of 5-HT from platelets in the presence of a low concentration of thrombin. These data suggest that platelet functions are regulated by the cytokines and that activated platelets participate in inflammatory process.

Blood Platelets↗
PubMed1991

Characterization of platelet aggregation induced by the human melanoma cell line HMV-I: roles of heparin, plasma adhesive proteins, and tumor cell membrane proteins.

We investigated the in vitro mechanism of platelet aggregation induced by HMV-I human melanoma cells. HMV-I cells, in the absence of exogenous plasma proteins, induced platelet aggregation, followed by the release reaction. Heparin at an anticoagulant concentration had no effect on the aggregation. Calcium ion was essential for this tumor cell-platelet interaction and could not be replaced by magnesium. Among the adhesive proteins containing RGD sequences that have been reported to enhance experimental metastasis, fibrinogen and thrombospondin significantly enhanced the aggregation induced by HMV-I cells, fibronectin and von Willebrand factor inhibited it, and vitronectin had no effect. To identify the platelet-aggregating factor(s) of the tumor cells, we have developed a monoclonal antibody against HMV-I cells that can inhibit HMV-I cell-induced platelet aggregation. Immunoprecipitation analysis revealed that this antibody recognized an Mr 71,000 membrane protein. These results suggest that the association between the tumor cells and platelets is mediated by the Mr 71,000 membrane protein recognized by this monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1991

Salivary excretion of mexiletine in normal healthy volunteers.

To investigate the kinetics and correlation between serum and saliva levels of mexiletine, serum (total and unbound) and saliva drug concentration-time courses have been analysed in five normal healthy volunteers after administration of a single oral dose (200 mg) of the drug. Mexiletine levels in saliva were always higher than those in serum. The drug concentration-time curve in each sample was analysed according to the non-linear least squares regression program MULTI, for a two-compartment model with first-order absorption. The saliva drug concentration in the post-absorption phase was found to be well correlated with either corresponding serum total or serum unbound drug level in four of the subjects. Although there was a large inter-individual variation in the ratio of saliva to serum drug concentrations as well as in the pharmacokinetic parameters, an almost consistent ratio was obtained in each individual.

Administration, Oral↗
PubMed1991

Pharmacokinetics of [6]-gingerol after intravenous administration in rats.

A high-performance liquid chromatographic method to determine [6]-gingerol, a pungent constituent of ginger, in rat plasma was developed and a pharmacokinetic study was performed in rats. Quantitative analysis with high reproducibility was achieved for [6]-gingerol over the concentration range of 0.2-40 micrograms/ml. After bolus intravenous administration at a dose of 3 mg/kg, the plasma concentration-time curve was described by a two-compartment open model. [6]-Gingerol was rapidly cleared from plasma with a terminal half-life of 7.23 min and a total body clearance of 16.8 ml/min/kg. Serum protein binding of [6]-gingerol was 92.4%.

Animals↗
PubMed1991

Enhanced entry of ciprofloxacin into the rat central nervous system induced by fenbufen.

The effects of fenbufen on the transport of ciprofloxacin (CPFX) into the brain and cerebrospinal fluid (CSF) were investigated in rats. Periodically after a bolus i.v. dose of CPFX (10 mg/kg), alone or with fenbufen (20 mg/kg), to rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the animal after sacrifice by microwave irradiation. Serum levels of CPFX in the terminal phase were significantly elevated by the coadministration with fenbufen. However, the extent of CPFX binding to serum protein was not affected by fenbufen. Immediately after the coadministration with fenbufen, brain and CSF levels of CPFX were raised by about 15 to 70% and 70 to 100%, respectively. Both brain/serum unbound and CSF/serum unbound level ratios were increased by fenbufen at relatively early periods after drug injection. Analysis based on physiological models indicated that fenbufen significantly increased the apparent diffusion clearances of CPFX across blood-brain and blood-CSF barriers. These findings suggest that coadministered fenbufen may facilitate the entry of CPFX into the central nervous system not only by elevation of serum level but also by enhancement of permeability across the blood-brain or blood-CSF barrier.

Animals↗
PubMed1990

Localization of von Willebrand factor and thrombin-interactive domains on human platelet glycoprotein Ib.

Platelet membrane glycoprotein Ib (GPIb) functions as receptors for thrombin and von Willebrand factor (vWF) in the presence of ristocetin. To precisely locate the domains on GPIb interacting with vWF and thrombin, we prepared several peptides that have amino acid sequences analogous to that of the GPIb alpha-chain and examined their effects on ristocetin-induced (vWF-dependent) and thrombin-induced platelet aggregations. A peptide extending from residues Asp235 to Lys262 showed the strongest inhibitory effect on ristocetin-induced platelet agglutination, and a group of overlapping peptides composed of 24-28 amino acid residues representing sequences extending from Phe216 to Asp274 was found to inhibit platelet aggregation induced by thrombin. Other peptides did not inhibit platelet aggregations. Moreover, the binding to platelets of the monoclonal anti-GPIb antibody (TM60) which had been shown to inhibit both ristocetin- and thrombin-induced platelet aggregations was strongly inhibited by a peptide extending from Asp249 to Asp274. These data demonstrate that the vWF-binding domain exists in a small region between residues Asp235 and Lys262; the thrombin-interacting domain, in contrast, is located between residues Phe216 and Ala274, with a possible center of interaction in the sequence from Phe216 to Thr240 on the GPIb alpha-chain, and thrombin binding requires a relatively strict conformation in this domain.

Antibodies, Monoclonal↗
PubMed1990

Localization of adhesive proteins in two newly subdivided zones in electron-lucent matrix of human platelet alpha-granules.

Platelet alpha-granules have been reported to consist of two zones, nucleoid and electron-lucent matrix, with different densities under electron microscopy. When washed human platelets were prepared by a rapid freeze-substitution method using liquid helium, we found that the electron-lucent matrix could be further subclassified into two zones having different densities: the intermediate and the light zones. The light zone was located at the periphery opposite the most dense nucleoid and contained several tubular structures with diameters of about 20 nm. The intermediate zone often laid between the nucleoid and light zone. By careful inspection, intermediate and light zones could even be identified in the platelets embedded in Lowicryl K4M, which where then used to localize several adhesive proteins in these two zone by immunocytochemical studies using the respective polyclonal antibodies. Fibrinogen, thrombospondin, and fibronectin were detected only in the intermediate zone. In contrast, von Willebrand factor (vWF) was localized only in the light zone, suggesting an association between vWF and the tubular structures in the light zone. In the nucleoid, none of these adhesive proteins were detected. Glycoprotein IIb/IIIa, a receptor for these adhesive proteins on the platelet surface, was detected not only on the outer surface of the cell membranes but also on the inner surface of the alpha-granule membrane. These data indicate that two zones with different densities in electron-lucent matrix and functions exist in the platelet alpha-granules.

Blood Coagulation Factors↗
PubMed1990

A possible reduction in the renal clearance of ciprofloxacin by fenbufen in rats.

The change in plasma concentration-time profile, serum protein binding and renal and biliary clearances of ciprofloxacin caused by coadministration of fenbufen has been studied in rats administered an intravenous dose of ciprofloxacin (5 mg kg-1) alone or with fenbufen (10 mg kg-1). Coadministered fenbufen significantly prolonged the plasma elimination half-life of ciprofloxacin from 40.5 to 57.6 min and tended to reduce the total body clearance of this quinolone by about 20%. The extent of ciprofloxacin binding to rat serum protein was not affected by fenbufen, nor did it affect the biliary clearance of the quinolone. However, fenbufen tended to reduce renal clearance and significantly decreased the cumulative renal excretion of the quinolone during at least the first 3 h after drug administration. These results suggest a possible reduction of ciprofloxacin clearance owing to inhibition of renal excretion by fenbufen.

Animals↗
PubMed1990

A minor possibility of pharmacokinetic interaction between enoxacin and fenbufen in rats.

In order to clarify the possibility of pharmacokinetic interaction between quinolone and fenbufen, the plasma concentration-time profiles and serum protein binding of enoxacin, fenbufen and its active metabolite, felbinac, were investigated in rats. The rats were administered an intravenous dose of enoxacin (5 mg/kg) and fenbufen (10 mg/kg) alone or concomitantly. Coadministration with fenbufen tended to prolong the plasma elimination half-life of enoxacin by about 20%, whereas it showed no effect on the area under plasma concentration-time curve, total body clearance or distribution volume of enoxacin. The extent of enoxacin binding to rat serum tended to be slightly reduced by fenbufen in vivo and in vitro. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected at all by the coadministration with enoxacin. These aspects suggest that there may be only a minor possibility of the pharmacokinetic interaction between enoxacin and fenbufen.

Animals↗
PubMed1990

High-performance liquid chromatographic determination of ciprofloxacin in rat brain and cerebrospinal fluid.

A novel high-performance liquid chromatographic method for the fluorometric determination of a newer quinolone, ciprofloxacin (CPFX), in rat brain and cerebrospinal fluid (CSF) was developed. CPFX in brain homogenate was extracted and injected onto a reversed-phase column without fluorescence derivatization. CSF was directly analyzed without the extraction procedure. Calibration curves were linear over the concentration ranges of 10 to 500 ng/g for brain and 5 to 500 ng/ml for CSF. The recoveries of CPFX added to brain were more than 97% with a coefficient of variation of less than 4%. The present method was sensitive and reliable enough to be utilized for detailed pharmacokinetic studies of CPFX in rat brain and CSF.

Animals↗
PubMed1990

[Three dimensional CT reconstruction image using a personal computer].

Three dimensional (3D) images were reconstructed from axial CT slices using the personal computer. Some devices of the program made it possible to decrease the image processing time and to produce the realistic images with cubic effect. The thresholding in the conventional 3 D imaging was not practical especially in the display of the soft tissues. The employment of the volume rendering technique and MRI data will give a clue to the solution of these problems.

Humans↗