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Biomedical subjects

H Shindo

Publications and source records attributed to H Shindo.

At least 127 records · Page 7Linked to original sources
PubMed1990

Isoliquiritigenin: a new aldose reductase inhibitor from glycyrrhizae radix.

Traditionally in Japan, some kampo medicines (traditional oriental herbal prescriptions) have long been used for the treatment of diabetic neuropathy. We have found that some aldose reductase inhibitors are included among these drugs. We further investigated the components of glycyrrhizae radix, a constituent of some kampo medicines, and isolated six compounds (GUs 9-17). Among these, GU-17, identified as isoliquiritigenin, had the most potent aldose reductase inhibiting activity. Isoliquiritigenin inhibited rat lens aldose reductase with an IC50 of 3.2 x 10(-7) M, using DL-glyceraldehyde as a substrate. It inhibited sorbitol accumulation in human red blood cells in vitro, with an IC50 of 2.0 x 10(-6) M. Isoliquiritigenin, when administered via an intragastric tube to diabetic rats, suppressed sorbitol accumulation in the red blood cells, the sciatic nerve, and the lens as effectively as ONO-2235. These results suggest that isoliquiritigenin may be effective in preventing diabetic complications.

Aldehyde Reductase↗
PubMed1990

Anti-platelet action of GU-7, a 3-arylcoumarin derivative, purified from glycyrrhizae radix.

We have purified GU-7, a 3-arylcoumarin derivative, from glycyrrhizae radix, which is a crude drug of kampo herbal medicines. This was identified to be a new chemical compound and was found to have an anti-platelet action. GU-7 inhibited platelet aggregation, phosphorylation of 40K and 20K dalton proteins, inositol 1,4,5-trisphosphate production, intraplatelet calcium increase and phosphodiesterase activity in vitro. The data indicate that GU-7 inhibits platelet aggregation by increasing intraplatelet cAMP concentration. We have already reported the existence of aldose reductase inhibitors in some kampo medicines. In addition to the aldose reductase inhibiting action, anti-platelet action may also explain the mechanism by which kampo medicines are effective to diabetic neuropathy.

Coumarins↗
PubMed1990

Clinical significance of erythrocyte sorbitol-blood glucose ratios in type II diabetes mellitus.

The polyol pathway has been implicated in the pathogenesis of diabetic complications. To determine the activity of the polyol pathway, the ratio of erythrocyte sorbitol to blood glucose, which reflects aldose reductase activity, was evaluated in 329 patients with type II (non-insulin-dependent) diabetes mellitus and in 100 nondiabetic age-matched control subjects. Although erythrocyte sorbitol levels were markedly elevated, sorbitol-glucose ratios were significantly lower in diabetic patients than in nondiabetic subjects. Sorbitol-glucose ratios in diabetic patients decreased progressively as blood glucose and hemoglobin A1c (HbA1c) levels increased. Sorbitol-glucose ratios were also studied during a 75-g oral glucose tolerance test. Ratios were again lower in diabetic patients than those in nondiabetic subjects and significantly decreased 120 min after glucose loading. The ratio in diabetic patients also fell with increasing age of the patients. In diabetic patients with neuropathy, retinopathy, or nephropathy, however, sorbitol-glucose ratios were significantly higher than in those without these complications; ratios increased further as complications became more severe. Our findings suggest that the affinity of aldose reductase for glucose in patients with diabetic complications may be increased and that the polyol pathway is implicated in the pathogenesis of diabetic complications.

Biomarkers↗
PubMed1990

Amplification and expression of a multidrug resistance gene in human glioma cell lines.

Two human glioma cell lines were examined for multidrug resistance (MDR). A vincristine (VCR)-resistant glioma cell line showed a cross resistance to Adriamycin (doxorubicin, ADR) and etoposide (VP-16) to varying extents, suggesting the presence of MDR; the resistance to VCR was considerably decreased by calcium entry blockers. On the other hand, another VCR-sensitive glioma cell line exhibited no cross resistance to ADR or VP-16. Double minute chromosomes and homogeneously staining regions as well as clonal aberrations of chromosome 7 were not observed in cytogenetic studies of multidrug-resistant and multidrug-sensitive glioma cell lines. In Northern and Southern blot analyses, MDR gene 1 (MDR1) messenger ribonucleic acid (mRNA) was shown to be overexpressed without any amplification of the MDR1 gene in multidrug-resistant glioma cell lines as compared to multidrug-sensitive glioma cell lines. It would be reasonable to suggest that amplification of the MDR1 gene may not be a sine qua non for acquisition of MDR and that the MDR1 mRNA level may be correlated with the extent of MDR.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Technique and usefulness of percutaneous transhepatic or trans T-tube cholangiolithotripsy (PTCL)].

Percutaneous Transhepatic or Trans T-tube Choledochal catheterization and lithotripsy were successfully performed without significant complication, using flexible forceps and electrohydraulic lithotriptor in all of seventeen cases. Eleven cases were treated by flexible stone forceps under the fluoroscopic control and the other six cases were treated by electrohydraulic lithotriptor under fiberscopic control. The age of the cases ranged from 47 to 79 (mean 65.4) years old. The main reasons why surgical operation was avoided were advanced age, previous history of cholecystectomy, and concurrent diseases.

Aged↗
PubMed1989

Lectin histochemistry of human gliomas.

Formalin-fixed and paraffin-embedded specimens of 24 human gliomas were examined histochemically with five lectins; concanavalin A (Con A), wheat germ agglutinin (WGA), Ricinus communis agglutinin 1 (RCA-1), peanut agglutinin (PNA), and Ulex europaeus agglutinin 1 (UEA-1). Although the staining intensity with lectins was variable, tumor cells in five astrocytomas, three oligodendrogliomas, six ependymomas, and one gliosarcoma, were generally positive for Con A, WGA, and RCA-1, and negative for PNA and UEA-1, whereas those in nine glioblastomas were usually positive for Con A and WGA and negative for RCA-1 and PNA as well as UEA-1. The malignancy in neoplastic astrocytes was correlated with the decrease in binding with lectins, especially RCA-1. Blood vessels, particularly the endothelial layers, in all gliomas were stained intensely with all lectins used. Macrophages showed two staining features with lectins; stippled and granular. The former macrophages were positive for Con A, WGA, RCA-1, and PNA, and negative for UEA-1, whereas the latter macrophages were positive for all lectins used. Thus, the staining characteristics with lectins of macrophages were different from those of any glioma cells and very useful for identification of macrophages in gliomas.

Brain Neoplasms↗
PubMed1989

Thienylpyrazoloquinolines with high affinity to benzodiazepine receptors: continuous shift from inverse agonist to agonist properties depending on the size of the alkyl substituent.

2-(5-Alkylthien-3-yl)-(1),2-(4-alkylthien-2-yl)-(2), and 2-(5-alkylthien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolines (3) were prepared in four steps starting from ethyl 4-chloroquinoline-3-carboxylate (4) and hydrazinothiophene-carboxylates 5, 8, and 9. All the assayed compounds possessed high affinities for benzodiazepine receptors (Ki = 0.3-2.6 nM). The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of pentylenetetrazole-induced convulsions, respectively. Introduction of alkyl groups of different sizes into the unsubstituted inverse agonistic compounds results in a corresponding shift in the activity from an inverse agonist to an antagonist to an agonist. The susceptibility of such a shift increases in the order of 1 less than 2 less than 3. This tendency may be explained by slight differences in the geometry of the alkyl substituents among the three series.

Animals↗
PubMed1989

The existence of aldose reductase inhibitors in some kampo medicines (Oriental herb prescriptions).

Traditionally in Japan, some kampo medicines which contain Glycyrrhizae radix (GR) and Paeoniae radix (PR) have long been used for the treatment of diabetic neuropathy. Since we have previously shown that GR und PR have potent aldose reductase inhibitory activities, we further investigated the constituents of these two. The boiled water extract of GR was applied to Sephadex LH-20 column chromatography and 6 fractions (Frs. A, B, Cs, Cp, D, and E) were obtained. Frs. Cp and D were retreated in the same manner and 7 pure compounds (GUs 1-7) were obtained. The boiled water extract of PR was fractionated with ethyl acetate followed by n-butanol and 3 fractions (Frs. 1-3) were collected. Fr. 1 was retreated in the same manner and 2 pure compounds (PRs 1 and 2) were obtained. Among the GU compounds, GU-2 was the most potent inhibitor of rat lens aldose reductase (RLAR) by inhibiting 86% at the concentration of 1.0 microgram/ml. The IC50 of GU-2 was 7.2 x 10(-7) M. Furthermore, GU-2 markedly inhibited sorbitol accumulation in human red blood cells, having an IC50 of 2.9 x 10(-5) M. GU-5 and PR-1 also inhibited RLAR (IC50: 5.6 x 10(-7) M and 6.3 x 10(-7) M, respectively). The structures of GU-2, GU-5, and PR-1 were identified as isoliquiritin, licuraside, and 1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

Effects of ML-9 on experimental delayed cerebral vasospasm.

Experimental delayed cerebral vasospasm was produced in a two-hemorrhage canine model. The spastic basilar artery was exposed via the transclival route under a surgical microscope and was dilated by the topical application of 1-(5-chloronaphthalenesulfonyl)-1H-hexa-1,4-diazepine (ML-9), a selective antagonist of myosin light chain kinase. Dilation was dose-dependent, with a median effective dose (+/- standard deviation) of 51.4 +/- 6.9 microM. In addition, 50 microM of ML-9 was injected into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, including a complete reversal of angiographic delayed vasospasm in three of seven dogs; in contrast, 150 microM of ML-9 was infused at 1.52 ml/min into the vertebral artery for 30 minutes, producing little dilation of the spastic basilar artery. In another study, the intracisternal perfusion of 50 microM of ML-9 at 1.48 ml/min for 30 minutes in dogs with an ICP of less than 200 mm H2O produced no serious electroencephalographic abnormalities, and the mean arterial blood pressure and pulse rate remained normal; no neurological deficits or significant histological abnormalities ascribable to the intracisternal ML-9 were found.

Administration, Topical↗
PubMed1988

Activation of brain function by S-135, a benzodiazepine receptor inverse agonist.

1. S-135, 2-(5-methylthien-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinoline-3- one, bind binds to benzodiazepine receptors with a high affinity and shows pharmacological actions opposite to those of conventional benzodiazepine drugs. 2. S-135 induced no convulsion in mice by itself, but selectively potentiated the effect of subconvulsive dose of pentylenetetrazole. 3. S-135 potentiated rat crossed extensor reflex and Ro 15-1788 completely antagonized this potentiation. 4. S-135 antagonized pentobarbital-induced anesthesia, tetrabenazine-induced ptosis and reserpine-induced hypoactivity and shortened immobilization time in the despair test in mice, indicating that this compound possesses antidepressive properties. 5. S-135 antagonized amnesia in mice and rats in passive avoidance tasks. 6. Glucose utilization in brain areas relating to memory and arousal functions was enhanced following S-135 treatment. 7. These results indicate that S-135 can be a useful drug for activating depressed brain function.

Animals↗
PubMed1988

Thienylpyrazoloquinolines: potent agonists and inverse agonists to benzodiazepine receptors.

Synthesis and structure-activity relationships of a series of 2-(thien-3-yl)- and 2-(thien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-ones are reported. A number of the compounds possessed 1 order of magnitude higher affinity for the receptors than diazepam. Planarity was one of the structural requirements for binding to benzodiazepine receptors. The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of the pentylenetetrazole-induced convulsions, respectively. Thien-3-yl compounds exhibited inverse agonist activity whereas thien-2-yl analogues with a 5'-alkyl group showed agonist activity. Substitution on the quinoline moiety did not enhance in vivo activity. The most potent compounds were the 5-methylthien-3-yl derivative 6a as an inverse agonist and the 5-methylthien-2-yl compound 13a as an agonist.

Animals↗
PubMed1988

Nuclear magnetic spectra of self complementary decanucleotides in solution; base sequence effect on the chemical shifts of nonexchangeable protons.

The aim of this study was to attempt to determine the extent to which the chemical shifts of the nonexchangeable base protons of a DNA helix depend upon the base sequence. We measured the proton NMR spectra of twelve decadeoxynucleotides in order to carry out a "statistical" treatment. In the helices, the chemical shifts were found to be determined within +/- 0.04 ppm, largely by the nearest neighbor residues on the 5'-side, and to a smaller extent by the residue on the 3'-side. The theoretical chemical shift calculations reproduced very well the polymerization shifts measured for H2 protons of adenosines if the electrostatic field effect was taken into account. A fair agreement was also obtained for H8 protons of the adenosine and guanosine residues. However, theory underestimates the polarization effects of the base protons of cytidine. This discrepancy suggests that the conformation of this residue is different in the mononucleotides relative to double helices.

Base Sequence↗