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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 325 records · Page 18Linked to original sources
PubMed1987

Determination of cefixime in biological samples by reversed-phase high-performance liquid chromatography.

A simple, accurate and precise isocratic reversed-phase high-performance liquid chromatographic method has been developed and validated for the determination of a new cephalosporin in human serum and urine. Human serum samples, calibration standards and quality control samples (250 microliter) were combined with an equal volume of 6% trichloroacetic acid (TCA). Human urine (0.1 ml) was combined with 6% TCA solution containing the internal standard. The compounds were detected by ultraviolet absorbance set to 280 nm for the serum assay and 313 nm for the urine assay. The method for the determination of cefixime in serum was linear from 100 ng/ml to 30.0 micrograms/ml (r = 0.999), and for the urine assay from 5 micrograms/ml to 100 micrograms/ml (r = 0.999). The minimum reportable quantity for the serum assay was 0.05 microgram/ml. The within- and between-day assay variation for both assays were found to be less than 10% in an extensive assay validation scheme. Results of a storage stability study indicated that human serum and urine samples could be safely stored for up to six months at -18 degrees C and three months at -10 degrees C, respectively.

Cefixime↗
PubMed1987

Pharmacokinetics of nilvadipine in healthy volunteers.

The pharmacokinetics of nilvadipine, a new antihypertensive and antianginal drug, were examined in healthy male volunteers. In a Latin square, three-way crossover design with a one-day run-in period, six subjects in three groups of two each were given single 2-, 4-, or 6-mg oral doses of nilvadipine after overnight fasting. Nilvadipine plasma concentrations up to 32 hours after drug treatment were determined by capillary column gas chromatography-negative-ion chemical ionization mass spectrometry (detection limit, 0.01 ng/mL). Nilvadipine urinary concentrations were determined by capillary column gas chromatography with electron capture detector (detection limit, 0.5 ng/mL). Nilvadipine plasma concentrations declined in a bi- or triexponential pattern after reaching the maximum plasma concentrations. The mean +/- standard deviation maximum plasma concentrations of 1.48 +/- 0.47, 3.48 +/- 0.53, and 6.69 +/- 1.54 ng/mL were attained from 1.08 to 1.50 hours after doses of 2, 4, and 6 mg, respectively. The elimination half-life was dose-independent and averaged 11.0 +/- 2.3 hours. The area under the plasma concentration-time curve increased in proportion to the dose. Nilvadipine was not detected in the urine. The pharmacokinetics of nilvadipine were generally linear over the dosage range studied. Besides the above model-independent pharmacokinetic parameters, model-dependent parameters were also obtained by curve-fitting the plasma data to a bi- or triexponential equation with zero-order absorption. Nilvadipine decreased blood pressure slightly and in a dose-dependent fashion.

Adult↗
PubMed1987

Effect of two different meals on bioavailability of nilvadipine in healthy volunteers.

The effect of two different meals on the bioavailability of nilvadipine, a new antihypertensive and antianginal drug, was examined in 16 healthy male volunteers in two separate studies. In each study of eight subjects in a Latin-square, two-way crossover design, two groups of four subjects each were given a single 6-mg oral dose of nilvadipine after overnight fasting or 30 minutes after a 464- or 748-kcal meal. There were no significant differences in the area under the plasma concentration-time curve or the maximum plasma concentration between the fasting and fed states for either meal. Although the time to reach the maximum plasma concentration was about the same after a 464-kcal meal and after fasting, it increased slightly but significantly after a 748-kcal meal, indicating possible delay in drug absorption after meals. These studies showed that the extent of bioavailability of nilvadipine appears to be little affected in the presence of food. Although a possible delay in the onset of absorption would occur, such a delay may not have any therapeutic importance in chronic therapy.

Adult↗
PubMed1987

Determination of (+)- and (-)-nilvadipine in human plasma using chiral stationary-phase liquid chromatography and gas chromatography-mass spectrometry, and a preliminary pharmacokinetic study in humans.

A stereoselective and sensitive method for the determination of nilvadipine, a new dihydropyridine calcium antagonist, in human plasma was developed. An internal standard, the deuterated analogue of racemic nilvadipine, was added to the plasma and extracted with an n-hexane:ethyl acetate (92.5:7.5) mixture under alkaline conditions. Each enantiomer in the extract was separated on a chiral stationary-phase column (Chiralpak OT(+)) for HPLC, and the effluents containing the respective isomers were collected. Each effluent was analyzed by fused-silica capillary column GC-electron capture negative ion chemical ionization MS. The mass spectrometer was set to monitor the molecular anions of nilvadipine and the internal standard. Calibration curves were linear for concentrations of each enantiomer from 0.025 to 10 ng/mL. The mean intra- and interassay precisions, as estimated by RSD, were less than 6% for each enantiomer. Assay suitability was assessed in a pharmacokinetic study in which four subjects were given a 6-mg oral dose of racemic nilvadipine. The t1/2 values of the two enantiomers were similar, but the AUC values of the more potent (+)-enantiomer were 2.4-3.6 times higher than those of its optical antipode.

Adult↗
PubMed1987

Pelvic lymph node metastasis of uterine cervical cancer.

The state of pelvic lymph node metastasis was observed in 627 cases of Okabayashi's radical hysterectomy performed from 1950 to 1984 of which 589 cases with a known 5-year survival rate were examined according to their relationship to prognosis. The incidence of lymph node metastasis was 29.7%, becoming progressively higher with succeeding clinical stages. The metastasis rates according to site were 6.9% hypogastric nodes, 4.9% obturator nodes, 4.4% iliac nodes, and 25.0% parametrial nodes. Among the factors considered in the postoperative classification, lymph node metastasis demonstrated high values in cervical infiltration cancer, positive parametrial infiltration, positive vaginal invasion, and infiltration into the uterine body and L type of CPL classification. The 5-year survival rate was 83.0% in negative cases of pelvic lymph node metastasis, while in positive cases, it was as poor as 45.8%. Considering the relationship of various factors, it is shown that the presence of lymph node metastasis has a great effect on prognosis.

Female↗
PubMed1987

Use of a series of ompF-ompC chimeric proteins for locating antigenic determinants recognized by monoclonal antibodies against the ompC and ompF proteins of the Escherichia coli outer membrane.

A method is presented for the efficient location of antigenic determinants using a series of chimeric proteins. By means of in vivo homologous recombination between the ompC and ompF genes coding for OmpC and OmpF, homologous proteins of the Escherichia coli outer membrane, a series of ompF-ompC chimeric genes was constructed (Nogami, T., Mizuno, T., & Mizushima, S. (1985) J. Bacteriol. 164, 797-801, and this work). The OmpF-OmpC chimeric proteins expressed by these genes were successfully used to locate antigenic determinants recognized by monoclonal antibodies, which specifically react with either the OmpC or OmpF protein. Interaction between monoclonal antibodies and the chimeric proteins was examined by means of either enzyme-linked immunosorbent assay or immunoblot analysis. The antigenic determinants recognized by three anti-OmpC antibodies and one anti-OmpF antibody were thus located. Finally, the polypeptides covering these regions were chemically synthesized for two of them and then tested as to their reactivity with the antibodies. The peptides reacted with the corresponding antibodies when the former were chemically coupled with bovine serum albumin. Most of the monoclonal antibodies isolated in this work were highly specific to the unfolded monomer of the protein against which the antibody was raised. But they did not react with the trimer, the native form. These results are discussed in relation to the structures and functions of the OmpC and OmpF proteins. The use of a series of monoclonal antibodies for studying the mechanism of protein translocation across the cytoplasmic membrane is also discussed.

Antibodies, Bacterial↗
PubMed1987

Phototropism in Hypocotyls of Radish : III. Influence of Unilateral or Bilateral Illumination of Various Light Intensities on Phototropism and Distribution of cis- and trans-Raphanusanins and Raphanusamide.

When etiolated radish (Raphanus sativus var. hortensis f. gigantissimus Makino) hypocotyls were subjected to a continuous unilateral illumination with white fluorescent light at 0.05, 0.1, or 1 watt per square meter, the suppression of the growth rate on the lighted side depended on the light intensity. The growth rate at the shaded side was only a little affected by the illumination at 0.05 and 0.1 watt per square meter but considerably suppressed by that at 1 watt per square meter. Upon a continuous unequal bilateral illumination, the growth rate was more strongly suppressed on the side of the higher intensity than on the side of the lower one, resulting in phototropic curvature toward the light source of the higher intensity. It was calculated from correlation analysis of light intensity and growth rate that, on an average, 6.9% of the irradiation applied to one side reached the opposite side. The amounts of cis- and trans-raphanusanins and raphanusamide in hypocotyls subjected to unilateral or unequal bilateral illumination increased much more at the side of the lighted or the higher intensity than at the opposite side. The present study demonstrates that phototropism in radish hypocotyl is correlated with and we conclude caused by a gradient of growth inhibition in the hypocotyl, depending on irradiation-induced amounts of cis- and trans-raphanusanins and raphanusamide.

Journal Article↗
PubMed1987

Phototropism in Hypocotyls of Radish: IV. Flank Growth and Lateral Distribution of cis- and trans-Raphanusanins in the First Positive Phototropic Curvature.

The first positive phototropic curvature induced by a pulse of unilateral white irradiation (0.1 watt per square meter, 30 seconds) of etiolated and de-etiolated Sakurajima radish (Raphanus sativus var hortensis f. gigantissimus Makino) hypocotyls was analyzed in terms of differential growth and growth inhibitor contents of the hypocotyls. In both etiolated and de-etiolated hypocotyls, the growth rates at the lighted sides were suppressed whereas those at the shaded ones showed no change. De-etiolation treatment induced a larger difference between the growth rates at the lighted and shaded sides of the hypocotyls, resulting in a larger curvature of de-etiolated seedlings than of etiolated ones. The contents of growth inhibitors, cis- and trans-raphanusanins, increased in the lighted but not in the shaded halves of the hypocotyls of etiolated seedlings. In de-etiolated seedlings, the two inhibitors increased due to the de-etiolation treatment. When de-etiolated seedlings were exposed to a pulse of unilateral irradiation the level of the two inhibitors remained high along the lighted side for 1 h following the light pulse, whereas at the shaded side the contents of the inhibitors abruptly decreased upon transfer to the dark, the difference between their amounts in the lighted and shaded sides being larger than in etiolated seedlings. Another growth inhibitor, raphanusamide, did not respond to the phototropic stimulus, although its amounts increased by the de-etiolation treatment. These data suggest that cis- and trans-raphanusanins are involved in the first positive phototropic response of radish hypocotyls, and that de-etiolation magnifies the phototropic response through induction of a larger lateral gradient of the raphanusanins in the hypocotyls by the phototropic stimulus.

Journal Article↗
PubMed1987

Use of bromocriptine in the treatment of normoprolactinemic infertility.

The efficacy of bromocriptine therapy was studied in 84 normoprolactinemic infertile patients. Bromocriptine (2.5-5.0 mg/day) was given for at least 1 month. Bromocriptine therapy was effective in 54 of 84 cases (64%), including 6 of 15 (40%) cases with amenorrhea, 16 of 24 cases (67%) with anovulatory cycle, 9 of 15 cases (60%) with delayed ovulation and 23 of 30 cases (77%) with luteal phase defect. Sixteen cases were able to conceive with bromocriptine alone. Twenty-five patients who did not respond to bromocriptine were treated with a combination therapy consisting of bromocriptine and clomiphene. Of the 25 cases, 14 responded to the therapy, and 6 of them were able to conceive. The response of prolactin to domperidone (10 mg, i.v.) was significantly (p less than 0.01) higher in the group responding to bromocriptine than in the nonresponding group. These results indicate that the administration of bromocriptine is an effective therapy for patients with normoprolactinemic endocrine disorders, and that domperidone may be useful in selecting the candidates for bromocriptine therapy.

Adult↗
PubMed1987

Metabolism of nilvadipine, a new dihydropyridine calcium antagonist, in rats and dogs.

1. The metabolic profiles of nilvadipine in the excreta of male rats and dogs were studied after i.v. and oral dosing. Six types of metabolites were isolated and identified from the urine of male rats and dogs or bile of rats. 2. Several metabolites were detected in the urine (12) and bile (17) of rats by two-dimensional t.l.c., after dosing with 14C-nilvadipine. The metabolic profiles in the excreta of rats and dogs were qualitatively similar but quantitative differences were observed. 3. The main metabolites were products of (i) oxidation of the 1,4-dihydropyridine ring to the corresponding pyridine, (ii) hydrolysis of the 5-isopropyl ester or 3-methyl ester group to carboxylic acid, and/or (iii) hydroxylation of the 6-methyl group or methyl group of the isopropyl ester chain. 4. Minor metabolites were products of hydrolysis from the 5-isopropyl ester to the carboxylic acid having a dihydropyridine ring, or reduction of the 3-nitro group of the phenyl moiety having a pyridine ring.

Animals↗
PubMed1987

Absorption, distribution and excretion of nilvadipine, a new dihydropyridine calcium antagonist, in rats and dogs.

1. The absorption, distribution and excretion of nilvadipine have been studied in male rats and dogs after an i.v. (1 mg/kg for rats, 0.1 mg/kg for dogs) and oral dose (10 mg/kg for rats, 1 mg/kg for dogs) of 14C-nilvadipine. 2. Nilvadipine was rapidly and almost completely absorbed after oral dosing in both species; oral bioavailability was 4.3% in rats and 37.0% in dogs due to extensive first-pass metabolism. The ratios of unchanged drug to radioactivity in plasma after oral dosing were 0.4-3.5% in rats and 10.4-22.6% in dogs. The half-lives of radioactivity in plasma after i.v. and oral dosing were similar, i.e. 8-10 h in rats, estimated from 2 to 24 h after dosing and 1.5 d in dogs, estimated from 1 to 3 d. In contrast, plasma concentrations of unchanged drug after i.v. dosing declined biexponentially with terminal phase half-lives of 1.2 h in rats and 4.4 h in dogs. 3. After i.v. dosing to rats, radioactivity was rapidly distributed to various tissues, and maintained in high concentrations in the liver and kidneys. In contrast, after oral dosing to rats, radioactivity was distributed mainly in liver and kidneys. 4. With both routes of dosing, urinary excretion of radioactivity was 21-24% dose in rats and 56-61% in dogs, mainly in 24 h. After i.v. dosing to bile duct-cannulated rats, 75% of the radioactive dose was excreted in the bile. Only traces of unchanged drug were excreted in urine and bile.

Animals↗
PubMed1987

Plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist, in man and dog.

The in vitro protein binding of nilvadipine, a new dihydropyridine calcium antagonist, was studied by equilibrium dialysis, ultracentrifugation, and equilibrium gel filtration. In the experiment with equilibrium dialysis, nilvadipine was highly bound to the plasma of man (97.5-98.7%) and dog (99.1-99.2%) with no plasma concentration dependency in a range of 10-100 ng/ml. Ultracentrifugation gave lower protein binding than that by equilibrium dialysis. From the experiments with equilibrium dialysis and equilibrium gel filtration, we found that lipoproteins and albumin are the main nilvadipine binding proteins in the plasma. The protein binding of nilvadipine in human plasma was unaffected or slightly decreased in the presence of therapeutic concentration of phenytoin, diazepam, salicylic acid, propranolol, quinidine and trichloromethiazide.

Animals↗
PubMed1987

Plasma levels of (+)- and (-)-nilvadipine after oral dosing with racemic (+)-nilvadipine in man.

The plasma levels of (+)- and (-)-nilvadipine 1 h after an oral dose of racemic (+)-nilvadipine 4 mg in sixteen healthy volunteers were studied to find the extent of variation between (+)- and (-)-nilvadipine plasma levels. Additionally the pharmacokinetic profiles of the enantiomers in the plasma up to 12 h after dosing were examined in three subjects. The plasma levels of the (+)- and (-)-nilvadipine in the three subjects peaked at 0.5-1 h, and the maximum concentration and the area under the plasma concentration-time curve of the more potent (+)-enantiomer were 2.38-3.18 and 2.27-3.10 times, respectively, higher than those of its optical antipode. The half-lives of the enantiomers were mostly similar. In the sixteen subjects, the ratio between (+)- and (-)-nilvadipine levels 1 h after dosing with racemic (+)-nilvadipine were from 1.77 to 3.65.

Administration, Oral↗