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Biomedical subjects

H Fujimura

Publications and source records attributed to H Fujimura.

At least 91 records · Page 5Linked to original sources
PubMed1987

[Screening test for calcium antagonist in natural products. The active principles of Uncariae ramulus et uncus].

We have previously reported on the Ca2+-blocking activity and active constituents of natural products. In the course of screening, Uncariae ramulus et uncus, a chinese herbal medicine, was found to possess such activity. In this paper, we attempted to characterize its active constituent which plays an important role in Ca2+-blocking activity. Its active principles were identified to be oxyindole-type alkaloids, rhynchophylline, corynoxeine, isorhynchophylline and isocorynoxeine, that showed inhibitory effects, similar to that of verapamil, on contractile response to high concentration of potassium ion (rats), CaCl2 (rats), norepinephrine in normal and Ca2+-free medium (rats and rabbits) and 45Ca2+-uptake (rats) in thoracic aorta with an activity two orders of magnitude less than the activity of verapamil.

Alkaloids↗
PubMed1987

[Role of the involvement of the reticular formation in the dementia of Parkinson's disease].

A post mortem study of 14 cases of Parkinson's disease was reported. Seven patients were mentally deteriorated and 7 were not, retrospectively. The semiquantitative study of the cortical lesions of senile dementia of Alzheimer type did not show any recognizable difference between the 2 groups. A greater degree of neuronal cell loss in the nucleus basalis of Meynert in the mentally deteriorated group was confirmed. The incidence of Lewy bodies in the brain stem reticular formation was remarkably increased in the mentally deteriorated group. A study of the reticular formation, including the raphe nuclei and the magnocellular nuclei of mid pons and upper medulla, revealed a significant higher incidence of Lewy bodies throughout the whole reticular formation in the mentally deteriorated group. The possible role of the lesions of the ascending reticular activating system in the mental deterioration is discussed.

Dementia↗
PubMed1986

Effects of crude drugs on experimental hypercholesterolemia. I. Tea and its active principles.

The effect of methanol extractives from tea leaves on hypercholesterolemia was examined in animal models. It was found that orally administered (-)-epicatechin gallate and (-)-epigallocatechin gallate from tea leaves lowered the serum cholesterol level in mice fed a high fat emulsion. Quantitation of tissue cholesterol and examination of liver tissues in mice fed a high cholesterol diet revealed that these constituents also significantly lowered the amount of cholesterol crystallization. These results support the reputed effectiveness of tea use in hypercholesterolemia.

Animals↗
PubMed1986

Analgesic and anti-inflammatory activities in rats of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its intestinal damage.

alpha-(3,5-Di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), an anti-inflammatory drug, possesses analgesic activity in rat models. In the acetic acid-induced writhing test, the oral ED50 values for KME-4, indomethacin, naproxen and ibuprofen were 5.2, 3.8, 7.0 and 18.6 mg kg-1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid-induced vascular permeability in rats. KME-4 also had analgesic activity in the tests of Randall-Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME-4 (10 mg kg-1 day-1 orally) has a preventive effect against adjuvant-induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg-1 day-1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME-4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen.

4-Butyrolactone↗
PubMed1986

[Central depressant effect of l-tetrahydroberberine-d-camphor sulfonate (THB-CS). Electroencephalographic study].

Effects of l-tetrahydroberberine-d-camphor sulfonate (THB-CS) on spontaneous EEG, arousal response and recruiting response were investigated in rabbits and rats in comparison with those of chlorpromazine. The spontaneous EEG recorded from the motor cortex and hippocampus showed a prominent resting pattern 3-5 min after intravenous administration of THB-CS in doses more than 0.01 mg/kg in rabbits and 30 min after oral administration of the drug in doses more than 1 mg/kg in rats. These effects lasted for 30-60 min after i.v. administration and 60-90 min after oral administration; however, the effects were not proportional to the doses up to 8 mg/kg (i.v.) and 12.5 mg/kg (p.o.). The abnormal characteristics of the EEG pattern such as seizure pattern and flattening were not observed. Chlorpromazine also produced the resting pattern in doses of 2 mg/kg (i.v.) in rabbits and 1 mg/kg (p.o.) in rats. THB-CS and chlorpromazine produced a slight elevation of threshold for the EEG arousal response elicited by high frequency stimulation of the midbrain reticular formation, but did not alter the recruiting response elicited by low frequency stimulation of the centromedian nucleus of the thalamus. These results suggest that the effects of THB-CS resemble those of chlorpromazine, but are different from those of barbiturates.

Administration, Oral↗
PubMed1986

[The mode of cardiac action of cardiotonic steroids isolated from Toad Cake in perfused working guinea-pig heart and effect of cinobufagin on experimental heart failure].

The effects of bufadienolides (bufalin, bufotalin, cinobufagin, cinobufotalin, gamabufotalin and resibufogenin) isolated from Toad Cake was compared to that of cardenolides (digitoxin and ouabain) on cardiac function in a guinea-pig working heart preparation. All the steroids showed the cardiotonic effect in a concentration-dependent manner, and the minimum threshold concentration was 10(-8) M for bufalin, cinobufagin, gamabufotalin and digitoxin and 10(-7) M for bufotalin, cinobufotalin and ouabain. In addition, the order of maximum efficacy of cardiotonic action was as follows: cinobufagin (3 X 10(-7) M) = ouabain (3 X 10(-7) M) greater than digitoxin (1 X 10(-7) M) = gamabufotalin (3 X 10(-7) M) greater than cinobufotalin (3 X 10(-7) M) greater than bufotalin (1 X 10(-7) M). The effect of cinobufagin was examined on experimentally induced heart failure caused by acute local ischemia through ligation of the left anterior descending coronary artery in perfused guinea-pig heart. Cinobufagin (3 X 10(-7) M) and digitoxin (1 X 10(-7) M) reestablished the coronary flow of perfused guinea-pig heart to 90% and 98% of the level prior to the coronary artery ligation. The cardiac output and left ventricular pressure of perfused heart were increased to the level prior to the acute local ischemia, and the left ventricular work was increased by cinobufagin (3 X 10(-7) M) and digitoxin (1 X 10(-7) M) to 108% and 106%, respectively, of the pre-ligation level. These results indicate that cinobufagin possesses strong cardiotonic action, similar, to digitoxin, in experimentally induced heart failure due to acute local ischemia.

Animals↗
PubMed1986

Comparative properties of SH-groups at mu, delta and kappa opioid receptor.

Crude synaptosomal membrane from rat brain was treated with three kinds of DTNB analogs. The receptor bindings of opioids were inhibited on a concentration dependent manner by 5-nitro-2-PDS and DTNHEB, regardless of the receptor types. DTNB showed complete inhibition of the bindings of mu and delta agonists. But, the effect of DTNB on the binding of kappa agonist was incomplete, resulting in approximately 50% inhibition at the maximal effective concentration. Treating the membrane with DTNB, but not with DTNHEB and 5-nitro-2-PDS, completely eliminated inhibitory effects of guanine nucleotides on agonist binding. These results suggest that one SH-group, being sensitive to DTNHEB, exists at an active center of the receptor binding site(R) and another SH-group, blocked by DTNB, forms a binding site for GTP in GTP-binding protein(Ni), and that a coupling mechanism between R and Ni at kappa receptor differs from those at mu and delta receptor.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 2nd communication: inhibitory effects on acute inflammation and prostaglandin-related reactions.

Since a newly synthesized nonsteroidal antiinflammatory drug (NSAID) having weaker effects on gastrointestinal tract, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), was found to markedly inhibit rat paw edema induced by carrageenin and other phlogists, the effects of the drug on other acute inflammatory reactions and prostaglandins (PGs)-related reactions were compared with those of known NSAID in this study. At even a large dose of CN-100, 20 mg/kg, the drug did not significantly inhibit the increased vascular permeability induced by histamine in rat skin, but CN-100 could dose-dependently inhibit the increased vascular permeability induced by acetic acid in mouse peritoneum. The inhibitory activity of CN-100 in the latter was equivalent to that of pranoprofen and indometacin. CN-100 exerted a potent inhibitory action on erythema induced by UV irradiation, which was equal to and 3 times stronger than pranoprofen and indometacin in activity, respectively. Since PGs participate in these acute inflammatory reactions, the effects of CN-100 on reactions relevant to PGs were examined. The drug at dose levels lower than antiinflammatory doses could prevent acute death and diarrhea induced by i.v. injection of arachidonic acid in rabbits and endotoxin in mice, respectively, suggesting that the drug had a potent inhibitory action on biosynthesis of PGs. The adverse effects of CN-100 on gastric and small intestinal mucosa was very weak, the activity being about one-tenth of that of pranoprofen and indometacin.

Animals↗
PubMed1986

Effect of the new antiallergic drug 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid on inflammatory reactions and platelet aggregation.

A new chemical compound, 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), known to have antiallergic activity was investigated with respect to its antiinflammatory effect. Sm 857 did not inhibit ultraviolet-induced erythema in guinea pigs, intradermal increased vascular permeability induced by histamine in rats and carrageenin-induced edema of the rat hind paw. Further, the compound showed no influence on wound healing in rats and was observed to exert neither analgesic nor inhibitory effect on platelet aggregation. Sm 857 was thus found to have no effect at all on acute and chronic inflammatory reactions. It was denied, therefore, that any antiinflammatory effect might be involved in the antiallergic effect of Sm 857 but it may be related to an inhibitory effect on the release of mediators or on some earlier stage. Therefore investigation was carried out into its inhibitory action on dextran- and compound 48/80-induced edema of the rat hind paw. As a result, Sm 857 showed a stronger inhibitory effect on dextran edema than tranilast. Sm 857 inhibited endotoxin-induced diarrhea in mice and the effect was similar to that of tranilast, suggesting its inhibitory action on the release of mediators.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 1st communication: inhibitory effects of rat paw edema.

In the development process of a new nonsteroidal antiinflammatory drug (NSAID) with less toxicity and side-effects, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepein-2-yl) propionic acid (CN-100) was chosen as the most excellent NSAID from synthetic tricyclic compounds after screening test. For the series of studies on antiinflammatory effects of this compound in detail, its effect on rat paw edema induced by various phlogists was first investigated. The inhibitory effect of CN-100 on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. The effect was not affected by continuous administration for 2 weeks or adrenalectomy. Similarly to indometacin, CN-100 had no significant effect on yeast-induced edema mediated by 5-hydroxytryptamine and concanavalin-A-induced edema unrelated with prostaglandins. However, CN-100 displayed a weaker inhibitory effect on nystatin-induced edema than indometacin, suggesting that CN-100 has a low membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. CN-100 inhibited the sustained edema induced by mustard, but the drug did not interfere with the increase in body weight of rats. Indometacin in the same dose caused decrease in body weight and death. The toxicity of CN-100 was definitely less than that of indometacin, although both drugs were similar in antiinflammatory activity and mode of action on rat paw edema. Results suggest that CN-100 is an effective drug on not only acute but also subacute and chronic inflammation.

Adrenalectomy↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 3rd communication: inhibitory effects on leucocyte emigration and proliferation of granulation.

The effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100), which has a significant inhibitory effect on acute inflammatory reactions, on leucocyte emigration and proliferation of granulation were examined in this study. The compound obviously inhibited the protein exudation and polymorph emigration 6 h after application of carboxymethylcellulose pouch method. It also definitely inhibited the monocyte emigration occurring 24 h after carrageenin pleurisy, and the inhibitory activity of the compound was nearly equal to that of pranoprofen and weaker than that of indometacin. CN-100 inhibited the proliferation of granulation in the test by paper disk method, i.e., the compound inhibited wound healing. The antigranulation activity of CN-100 was also nearly equal to that of pranoprofen and weaker than that of indometacin. These results proved that CN-100 should definitely inhibit the reactions of the second and third inflammatory phases of the whole reactions from the exudative phase throughout proliferative phase, suggesting that the compound is a useful antiinflammatory drug.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl]propionic acid. 4th communication: inhibitory effects on rat adjuvant arthritis.

The preventive and therapeutic effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100) on local and systemic changes of rats with adjuvant arthritis being used frequently as experimental model of rheumatoid arthritis were investigated in comparison with those of reference drugs, indometacin and pranoprofen. Preventively and therapeutically CN-100 showed potent inhibitory effects on adjuvant primary inflammation and secondary lesion. CN-100 also exerted an evident preventive effect on destruction of foot bone, improved the changes in organ weight, and stimulated weight gain. These effects were dose-dependent, and the effects at 5.0 mg/kg were almost the same as those of indometacin and pranoprofen at 1.25 and 2.5 mg/kg, respectively. The mode of action of CN-100 resembled that of reference compounds. Although CN-100 improved the change in albumin/globulin ratio, which was a parameter of systemic inflammatory reactions, the effect was more remarkable in therapeutic administration than in preventive one. This suggests that CN-100 is suitable for clinical application.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 5th communication: antiplatelet effect of the drug and antiinflammatory effect of its main metabolite.

Since nonsteroidal antiinflammatory drugs (NSAID) usually have an antiplatelet effect, the inhibitory effect of 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl) propionic acid (CN-100), which exerts a potent antiinflammatory effect, was compared with those of reference drugs, indometacin and pranoprofen, in this study. Indometacin at 10(-5) mol/l inhibited completely (100%) rat and rabbit platelet aggregation induced by collagen and arachidonic acid. Pranoprofen at 10(-5) mol/l also entirely inhibited rat platelet aggregation induced by the two aggregators, but an about 10 times higher concentration was required to produce 100% inhibition of rabbit platelet aggregation. CN-100 at 10(-5) mol/l exerted 100% inhibition of rat platelet aggregation induced by collagen, whereas more than 10(-4) mol/l was needed to exhibit 100% inhibition of aggregation induced by arachidonic acid and ADP. The inhibitory activity of CN-100 on aggregation of rat platelets ex vivo was weaker than those of reference NSAID, i.e., the antiplatelet effect of CN-100 was found to be weak. The main metabolite of CN-100 also had a weak antiplatelet effect, and its antiinflammatory effect on carrageenin edema and UV erythema was apparently weaker than that of CN-100. The inhibitory effect of the metabolite on endotoxin diarrhea was weak. The ulcerogenic effect of the metabolite on gastric mucosa was similar to that of CN-100, but the effect rarely seemed to be a clinical problem because it was basically weak.

Animals↗
PubMed1986

Study of drug interaction between the new antiallergic drug 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid and theophylline.

A new chemical compound, 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), known to inhibit the second stage type I allergy and endowed with antiasthmatic action, was investigated with regard to its effects on theophylline (TP) blood level in comparison with ketotifen and tranilast, antiasthmatics of the same therapeutic category as Sm 857, and tiaramide, an antiinflammatory agent. Sm 857 was administered orally to rats at 50 mg/kg, followed by oral administration of TP at 10 mg/kg or intravenous administration of aminophylline 13 mg/kg 10 min later. The concomitant use of Sm 857 apparently lowered the development of TP blood level during 1-5 h after administration when compared with the control. A similar lowering effect on TP blood level was observed at both single and 3-day prior administration of Sm 857. Ketotifen also reduced TP blood level at a dose of 50 mg/kg, while tranilast proved to have almost no such influence on TP blood level. Unlike the mentioned antiasthmatics, tiaramide tended to delay TP clearance. The determination of TP free fraction produced by addition of testing drugs to TP-containing rat serum in vitro after incubation for a certain period of time revealed a 30% increase in free fraction percent in case of Sm 857 addition, 7% increase in case of tranilast addition and no change at all in case of ketotifen and tiaramide addition. Above results suggest that the concomitant use of Sm 857 and TP might cause drug interaction. Sm 857 is thought to increase the blood free fraction of concomitantly used TP and to accelerate elimination of TP from blood.

Aminophylline↗
PubMed1985

Interaction of BW755C, a potent inhibitor of lipoxygenase and cyclo-oxygenase, with mitochondrial cytochrome oxidase.

The interaction between BW755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline), a potent inhibitor of both lipoxygenase and cyclo-oxygenase, and respiratory chain in mitochondria and electron transport particles (ETP) from rat livers was examined. BW755C accelerated the oxygen uptake by mitochondria without the addition of substrate for the respiratory chain. Spectrophotometric study revealed that BW755C was quickly oxidized by cytochrome oxidase in mitochondria to a compound possessing an absorption maximum at 524 nm. p-Phenylenediamine (p-diaminobenzene, PPDA), which, like BW755C, serves as an electron donor to cytochrome oxidase, was shown to inhibit the generation of active oxygen in macrophages; the inhibition was stronger than that of BW755C. These results strongly suggest that the oxidative conversion of BW755C by mitochondrial cytochrome oxidase is associated with its potentially inhibitory action on the active oxygen-generating system in phagocytes.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗