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H Shimamura

Publications and source records attributed to H Shimamura.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evaluation of drug disappearance from nasal cavity by the deposit method.

In order to evaluate antiallergic intranasal formulations, the rates of drug disappearance from rat nasal cavity were estimated by the deposit and perfusion methods. The deposit method, which estimates changes in the amount of residual drug in the nasal cavity following washout of the deposited drug over time after application, yielded a good correlation between apparent disappearance rate constant and the combination of lipophilicity and molecular weight. Since the deposit method can be used only with delivery of small amounts of drug to the nasal cavity, the physiological characteristics of the nasal membrane readily affect drug disposition in tests performed with it, and adsorptive drugs such as parabens exhibited rapid disappearance. Doses used clinically for intranasal administration are usually small, and in the case of antiallergic formulations, it is important to maintain the drug concentration in the nasal mucous membrane. The deposit method should be useful for evaluating intranasal antiallergic drug formulations.

Administration, Intranasal↗
PubMed1998

Suppression of the SOS-inducing activity of Trp-P-1 and aflatoxin B1 by meso-dihydroguaiaretic acid from Machilus thunbergii in the Salmonella typhimurium TA1535/pSK1002 umu test.

The methanol extract from Machilus thunbergii showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes. The methanol extract from M. thunbergii was successively re-extracted with chloroform, butanol and water. A suppressive compound in the chloroform extract fraction was isolated by SiO2 column chromatography and identified as meso-dihydroguaiaretic acid by GC-MS, and 1H- and 13C-NMR spectroscopy. Meso-dihydroguaiaretic acid inhibited of the SOS-inducing activity of Trp-P-1 in the umu test. Gene expression was suppressed by 62% at less than 0.18 mumol/ml, the ID50 value being 0.08 mumol/ml. Compound 1 was also assayed with aflatoxin B1 (AfB1) and showed a suppressive effect.

Aflatoxin B1↗
PubMed1997

Mutational specificity of the ferrous ion in a supF gene of endonuclease III/VIII deficient Escherichia coli.

When 125 microM Fe2+/EDTA treated plasmid pUB3 was used to transfect an Escherichia coli NKJ2004 (nth nei) host, which is totally defective in glycosylases for thymine glycol and 5-hydroxycytosine, a 3.7 fold increase in mutation frequency was observed. Among 46 supF mutants sequenced, 28 had base substitutions, with G:C-->C:G transversion predominant (14 cases), followed by G:C-->T:A transversion (6 cases) and G:C-->A:T transition (6 cases). The results are consistent with our previous Fe2+ mutagenesis results where, in the wild type host, 78% were base substitutions, with G:C-->C:G transversion (59%) predominant, followed by G:C-->T:A transversion (28%) and G:C-->A:T transition (11%). Treatment of pUB3 DNA with Fe2+/EDTA did not yield formation of Endonuclease III sensitive sites. The possibility of 5-hydroxycytosine as the causative lesion for Fe2+ induced G:C-->C:G transversion is discussed.

DNA Repair↗
PubMed1996

Pharmacokinetics and polymorphic oxidation of dextromethorphan in a Japanese population.

The plasma concentration and cumulative urinary excretion over 34 h of dextromethorphan, free and conjugated dextrorphan, and 3-hydroxymorphinan were determined in seven healthy Japanese subjects after oral administration of 30 mg dextromethorphan hydrobromide. Conjugated metabolites were extensively present, whereas no detectable dextromethorphan or free metabolites were observed in the plasma of any subject. On average, 72% of the dose was excreted in urine within 34 h. This was detected mainly as conjugated metabolites with only slight traces of dextromethorphan and free metabolites. From the time-courses of the metabolic ratio (the ratio of urinary output of dextromethorphan to dextrorphan), the metabolic ratios seemed to become constant 7.5 h after oral administration. Phenotyping was performed using metabolic ratios in 75 unrelated healthy Japanese subjects (43 males and 32 females). The logarithmic metabolic ratio was bimodally distributed and one subject (1.3%) was identified as a poor metabolizer.

Administration, Oral↗
PubMed1996

Establishment of an experimental liver metastasis model by intraportal injection of a newly derived human pancreatic cancer cell line (KLM-1).

CONCLUSION: It is suggested that this liver metastasis model formed by a highly metastatic variant (KLM-1) is valuable for the study of the liver metastatic processes of human pancreatic cancer. BACKGROUND: Liver metastasis in the early postoperative period is one of the causes for the poor prognosis of patients with resected pancreatic cancer. Therefore, it is necessary to establish an experimental model to study the mechanisms of liver metastasis in pancreatic cancer. METHODS: Human pancreatic cancer cell lines (PK-1, PK-9, and KLM-1) were injected into the portal vein of nude mice with or without pretreatment with antiasialo GM1, and colonies of liver metastases were counted for comparison of metastatic ability of these cell lines. Biological and histopathological characteristics of the highly liver metastatic cell line (KLM-1) were compared with its parent cell line (PK-1). RESULTS: PK-1 cells and PK-9 cells rarely formed liver metastasis foci, but pretreatment with antiasialo GM1 promoted liver metastasis. KLM-1 cells formed liver metastases at the rate of 70% even without antiasialo GM1 pretreatment. KLM-1 cells had such biological characteristics as short doubling time, short lag phase, and resistance to NK cytotoxicity. After intraportal injection of 125I-labeled KLM-1 cells, radioactivity as well as micrometastases were detected in the liver at 72 h.

Animals↗
PubMed1996

Biliary excretion of glycyrrhizin in rats: kinetic basis for multiplicity in bile canalicular transport of organic anions.

PURPOSE: To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides. METHODS: GR was administered intravenously as a bolus to Sprague-Dawley (SD) rats which received an i.v. infusion of inhibitors (dibromosulfophthalein (DBSP) and indocyanine green (ICG)) at their transport maximum rates. Biliary excretion of GR was also examined in Eisai hyperbilirubinemic rats (EHBR), which have a hereditary defect in the canalicular transport system of several organic anions. RESULTS: Infusion of ICG did not affect the biliary excretion of GR, whereas infusion of DBSP reduced it significantly. The plasma concentration of GR was increased by DBSP but not by ICG. In EHBR, the biliary excretion of GR was severely impaired, resulting in an increase in the plasma concentration of GR. CONCLUSIONS: These findings suggest (1) that the biliary excretion of GR is mediated by the system which is shared by DBSP and LG glucuronides but not by ICG and (2) that this system is hereditarily defective in EHBR. Together with our previous findings, the multiplicity for the biliary excretion of organic anions is shown.

Animals↗
PubMed1996

N30 in PD.

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Brain↗
PubMed1996

Central conduction in somatosensory evoked potentials: comparison of ulnar and median data and evaluation of onset versus peak methods.

To compare central conduction in ulnar and median nerve somatosensory evoked potentials (SEPs), we recorded SEPs from the neck and scalp elicited by median and ulnar nerve stimulation in 46 normal young adults. We determined the central conduction time (CCT) in each subject from peak-to-peak and onset-to-onset measurements. The mean value of the onset CCT for the ulnar nerve SEP was 6.2 +/- 0.3 msec, and for the median nerve SEP, 5.9 +/- 0.3 msec. Onset CCT was significantly longer for the ulnar nerve SEP, and there was a significant correlation between onset CCT in both median and ulnar nerve SEPs and subject height. In contrast, the mean value of the "conventional" peak CCT for the ulnar nerve SEP was 5.6 +/- 0.6 msec, and for the median nerve SEP, 5.8 +/- 0.5 msec, with no significant difference between them. In addition, the peak CCT was not correlated with subject height in the ulnar or median nerve SEPs. Our findings suggest that onset CCT measurement is superior to the conventional peak CCT measurement for ulnar as well as median nerve SEPs, and confirm that the central conduction pathway for the ulnar nerve SEP is slightly longer than that for the median nerve SEP.

Adolescent↗
PubMed1995

Studies on antiulcer agents. II. Antiulcer properties of N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides inhibiting release of histamine from passively sensitized rat peritoneal mast cells.

With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.

Animals↗
PubMed1995

Studies on antiulcer agents. I. Synthesis and pharmacological properties of ethyl 2-[(1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate, a new H+/K(+)-ATPase inhibitor possessing mucosal protective activity.

Ethyl 2-[1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate (2) has been synthesized and evaluated for antiulcer properties. Compound 2 is a H+/K(+)-ATPase inhibitor that affords mucosal protection against absolute ethanol-induced gastric lesions in rats after oral and parenteral administrations. On the other hand, omeprazole, a representative H+/K(+)-ATPase inhibitor, showed mucosal protective action only after oral administration, indicating that it required gastric acid secretion to generate activity. The antiulcer activity of 2 in animal models, such as water-immersion stress-induced gastric ulcer in rats and acidified aspirin-induced gastric ulcer in rats, was three times higher than that of cimetidine.

Animals↗
PubMed1995

Studies on antiulcer agents. IV. Antiulcer effects of 2-benzylthio5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds.

With a view to finding more effective antiulcer agents, a series of 2-benzylthio-5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds were synthesized and evaluated in a histamine-stimulated gastric secretion model. The sodium salt of the 2-(dimethylamino)benzylthio derivative (8) showed gastric mucosal protection and gastric antisecretion activities, and was also effective against experimental gastric and duodenal ulcers induced by some ulcerogenic agents. Based on a comparison of the antiulcer properties of 8 with those of the lead compounds (1 and 2) and cimetidine, it appears that, for improvement of antiulcer activity, the reduction of gastric acidity is a more important factor than the reduction of gastric volume output or gastric total acid output.

Animals↗
PubMed1994

Variability in absorption lag time of pyridoxal phosphate under fasting and pre- and post-meal conditions.

Inter-individual variations in the absorption lag time of pyridoxal phosphate were determined after administration of an enteric-coated tablet (EC) or a plain capsule (PC) to 113 healthy volunteers under fasting, pre-meal, and post-meal conditions. The absorption lag time of pyridoxal phosphate was assessed from the urinary excretion of 4-pyridoxic acid after administration of EC and PC. Significantly larger lag times after administration of both formulations were observed under post-meal conditions than under pre-meal conditions (0.477 +/- 0.315 h versus 0.081 +/- 0.086 h for PC and 1.995 +/- 1.345 h versus 1.064 +/- 1.327 h for EC), indicating that the mean gastric emptying rates of both a solution and a tablet were delayed after food intake. The lag time for PC showed little inter-individual variation with (0-1.2 h) or without food (0-0.25 h), whereas that for EC showed markedly large inter-individual variation, from 0.25 to 2.63 h (median, 1.5 h) in the fasting condition, from 0.25 to > 5.5 h (median 0.25 h) under pre-meal conditions, and from 0.25 to > 5.5 h (median 1.25 h) under post-meal conditions. The effect of food on the gastric emptying rate of a solution appears to be almost uniform, whereas that for a tablet is so unpredictable that a reliable absorption rate for an enteric-coated tablet cannot be expected, particularly under pre- and post-meal conditions.

Absorption↗
PubMed1994

Multiple systems for the biliary excretion of organic anions in rats: liquiritigenin conjugates as model compounds.

Liquiritigenin (LG), 2, 3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)-(S)-4H-1-benzopyran-4-1, is metabolized to five kinds of conjugates (glucuronides and sulfates) that are excreted predominantly into the bile (Shimamura et al., 1993). Using LG as a model compound, we studied the multiplicity for the biliary excretion of conjugates in vivo. LG was administered i.v. as a bolus to Sprague-Dawley rats (SD rats) that received i.v. infusions of the inhibitors [glycyrrhizin (GR), dibromosulfophthalein (DBSP) and indocyanine green (ICG)] at their maximal transport rates. The infusion of GR and that of DBSP reduced significantly the biliary excretion of all the conjugates except LG 4',7-O-disulfate (M3), whereas infusion of ICG did not affect the excretion of conjugates. To minimize the effect of the other tissues on the disposition of the conjugates, the apparent biliary excretion clearance (CLbile,app) was calculated. The CLbile,app values of LG 4'-O-glucuronide (M1), LG 7-O-glucuronide (M2), LG 4'-O-glucuronide 7-O-sulfate (M4) and LG 7-O-glucuronide 4'-O-sulfate (M5) were significantly reduced by GR and DBSP infusion, whereas the CLbile, app value of M3 was not affected by these inhibitors. The CLbile, app values of all the conjugates except M2 were not reduced by ICG infusion. In Eisai hyperbilirubinemic rats, which have a hereditary defect in the canalicular transport system for several organic anions, the biliary excretion clearance of M1, M2, M4 and M5 was markedly reduced, whereas that of M3 was comparable with that in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Identification of tissues responsible for the conjugative metabolism of liquiritigenin in rats: an analysis based on metabolite kinetics.

We kinetically examined tissues responsible for the conjugative metabolism (glucuronidation and sulfation) of a component in a crude drug, liquiritigenin (LG; 2,3-dihydro-7-hydroxy-2-(4- hydroxyphenyl)-(S)-4H-1-benzopyran-4-one) in rats in vivo. LG has been found to form five kinds of conjugates (4'-O-glucuronide (M1), 7-O-glucuronide (M2), 4',7-O-disulfate (M3), 4'-O-glucuronide-7-O-sulfate (M4) and 7-O-glucuronide-4'-O-sulfate (M5)). Analysis based on metabolite kinetics [K. S. Pang, J. Pharmacokin. Biopharm., 13, 633 (1985)] of the area under the plasma concentration curves (AUCplasma) and cumulative biliary excretions (Aibile) of the ligands after intravenous or hepatic portal venous administration of LG revealed that the liver has the ability to generate all the metabolites. For M1 and M2, the apparent biliary excretion clearance (CLbile,app) obtained by dividing the biliary excretion rate for the metabolite by the plasma concentration of the metabolite decreased with time, confirming that M1 and M2 were formed in the liver. To further analyze the formation rate constants for metabolites in each tissue, we measured the ligand content in several tissues after intravenous administration of LG. By correcting the content of metabolites that were taken up from the plasma, we found that the formation rates per gram of tissue were largest in the liver, except for M3. The metabolic capability of the kidney for M1 and M2 was 15% and 60%, respectively, to that of the liver whereas for M3, the metabolic ability of the kidney was 2.5-fold greater than that of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Rapid recovery of chronic inflammatory demyelinating polyneuropathy induced by steroid pulse therapy--changes in nerve conduction].

A 47-year-old female patient with chronic inflammatory demyelinating polyneuropathy started to recover from her numbness and weakness within a few hours following the commencement of intravenous methylprednisolone 1,000 mg. In parallel with the recovery of muscle strength, a prolonged latency time of the M-wave was normalized within a day by a revival of the new motor units with a normal latency. In many cases with CIDP, it has been recognized that the gradual decrease in latency time over weeks is a later phenomenon following early increase in amplitude of the M-wave during recovery of weakness, which is explained by remyelinating process. On the other hand, the revival of motor units with a normal latency time from demyelinating conduction block is difficult to explain by remyelinating process, because remyelinating fibers usually have a very slow conduction velocity. Some minor morphological changes of paranodes or humoral factors may be partly responsible for development conduction block in CIDP.

Chronic Disease↗