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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

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

Response rate and cell-cycle changes due to intra-arterial infusion chemotherapy with cisplatin and bleomycin for locally recurrent uterine cervical cancer.

Intra-arterial infusion with cisplatin (CDDP) and bleomycin (BLM) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone. Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM. Two to four courses of the infusion therapy were given to each patient, and the response rate, the tumor and serum drug concentrations, and the cell kinetics in tumor tissue were evaluated. The response rate (CR+PR) was 71.4% according to the WHO criteria. There was no difference, in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders. Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment, both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors. These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy.

Adult↗
PubMed1992

Evaluation of measurement of fetal crown-rump length from ultrasonically timed ovulation and fertilization in vitro.

To assess with accuracy the development and maturity of the fetus, we evaluated fetal growth in 46 pregnant women who had conceived subsequent to ultrasonically timed ovulation. Fetal crown-rump length (CRL) was measured at gestational ages that differed by about 1 day from those previously reported. The variance in CRL measurements at each gestational age was small, and the data were normally distributed. The CRL growth curves of this and previous studies were tested using measurements from 7 pregnancies derived from in vitro fertilization (IVF). The data from IVF pregnancies were consistent with our curve, having 1 day difference to those previously reported. The gender of the fetus did not influence the CRL during the first trimester. The results suggest that fetal growth is uniform during the first trimester.

Embryonic and Fetal Development↗
PubMed1992

Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration.

Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol.

Aging↗
PubMed1992

[A case of optic neuritis associated with anticardiolipin antibodies].

We reported a case of optic neuritis with the persistence of severe visual loss and central scotoma in a 26-year-old woman who was proven to have biologic false positive test for syphilis, and the elevated serum titres of IgG and IgM anticardiolipin antibodies. C.S.F. findings showed the absence of oligoclonal bands and the presence of IgM anticardiolipin antibody. She was treated twice at intervals of two weeks with methylprednisolone 1000 mg intravenously daily for three days (pulse therapy), and was started on oral prednisolone 60 mg daily which tapered gradually. After the second treatment of the pulse therapy, her visual acuity was improved remarkably and the titre of anticardiolipin antibodies became normal. Her clinical course seemed to be different from that of the optic neuritis of multiple sclerosis, in which many of patients recover near normal visual acuity after a first attack. We suggested that antiphospholipid antibodies might play a role in the etiology of her optic neuritis.

Adult↗
PubMed1991

Polysaccharide-coated oil droplets in oil-in-water emulsions as targetable carriers for lipophilic drugs.

Surface of oil droplets in an oil-in-water (o/w) emulsion were coated with naturally occurring polysaccharides (such as mannan, amylopectin, and pullulan) which were, in part, bearing a cholesterol moiety. The mean size of the colloidal droplets was not altered much, even by coating with the polysaccharide derivatives, while the surface charge of the droplet decreased upon coating. Mannan and amylopectin derivative-coated droplets aggregated upon addition of Concanavalin A. These observations suggest that the terminal sugar moiety of the specific polysaccharides on the surface of colloidal droplets can be recognized by lectin. After intravenous injection of the emulsions into guinea pigs, kinetics of the blood clearance and the tissue distribution of the polysaccharide-coated oil droplets, which contain [14C]coenzyme Q10 as the marker, were investigated. In the initial rapid phase of blood clearance of the radioactivity, the polysaccharide-coated droplets were cleared from the blood stream slower than the uncoated ones. The lung uptake of the mannan derivative-coated droplet emulsion at 30 min after intravenous injection was approximately 15 times higher than that of the conventional emulsion without the polysaccharide coat.

Animals↗
PubMed1991

Improvement in the proliferative activity of human-human hybridomas at low cell density by transfection with bFGF gene.

Highly purified recombinant basic fibroblast growth factor (rbFGF) and acidic FGF (aFGF) stimulated the proliferation of human-human (h-h) hybridomas to the extent of over four-fold from a low cell density such as 1 x 10(3) cells per ml in a serum-free medium in 24-well plates. The stimulatory effect of rbFGF was also observed in various lymphoid cell lines. Expecting that FGF could be an autocrine growth factor, we introduced bFGF gene into a h-h hybridoma using an expression plasmid induced by dexamethasone. The transformed cells thus obtained, HPO-75.11 bFGF-7, were able to grow well from a low inoculum density in a serum-free medium and antibody production was also increased when bFGF gene expression was induced. The transformed cells could grow at clonal density in a serum-free medium in 96-well plates, though the original cells could not. We also obtained a more practical transfectant, HPO-75.29-H74, using a high-shear stress adapted clone as the recipient and an expression plasmid having bFGF gene under the control of metallothionein-I promoter. The HPO-75.29-H74 cells were capable of growing and producing human monoclonal antibody against hepatitis B virus surface antigen from an inoculum density of 1 x 10(3) cells per ml in an agitation vessel without addition of an inducer.

Animals↗
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↗
PubMed1991

[A case of Günther vena caval filter insertion for recurrent pulmonary embolism].

We report that the Günther vena caval filter was successfully inserted in a case of recurrent pulmonary embolism resulting from ilio-femoral venous thrombosis. A 42-year-old woman was admitted to Osaka City University Medical School Hospital for dyspnea and chest pain on April 19, 1988. Pulmonary perfusion scintigraphy and pulmonary arterial angiography proved pulmonary emboli. The combination therapy of heparin and urokinase was performed, and her condition markedly improved. Then an ilio-femoral venography revealed only iliac vein compression but no thrombi. Therefore she was followed as an out patient with anticoagulant therapy. Nevertheless on April 10, 1989 she was admitted again complaining dyspnea and cyanosis. By venography at this time, some filling defects due to thrombi in right iliac vein were found. Therefore, we decided the insertion of the Günther vena caval filter for recurrent pulmonary embolism using Seldinger method via right internal jugular vein. We expect that the Günther vena caval filter will be useful for preventing pulmonary embolism resulting from ilio-femoral venous thrombosis because its procedure is easy, non-invasive and without significant complications.

Adult↗
PubMed1990

Synthesis and characterization of 1,2-dimyristoylamido-1, 2-deoxyphosphatidylcholine as an artificial boundary lipid.

The synthesis and characterization of an artificial boundary lipid, 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine (DDPC), are described. DDPC has two amide bonds instead of ester bonds of regular lecithins such as 1,2-dimyristoylphosphatidylcholine (DMPC). In differential scanning calorimetry (DSC) measurements, DDPC gave two endothermic peaks: one was at 18.0 degrees C (delta H = 10.74 kJ.mol-1) and the other at 23.0 degrees C (delta H = 12.91 kJ.mol-1). The former peak was sharp and considered to be the phase transition of the hydrocarbon region, while the latter was assigned to the melt of the hydrogen-belt formed by the amide groups of DDPC. Addition of DDPC to DMPC made the DMPC membrane less fluid in the region close to the surface, and significantly increased the reconstitution efficiency of glycophorin into the membrane. This effect of DDPC was much larger than that of naturally occurring lipid, sphingomyelin.

Animals↗