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Biomedical subjects

H Fujimura

Publications and source records attributed to H Fujimura.

At least 199 records · Page 11Linked to original sources
PubMed1983

[Influence of indomethacin and clidanac on the blood pressure lowering effect of beta-blockers].

In conscious rabbits, the intravenous administration of pindolol (1.25 mg/kg), propranolol (1 mg/kg) and alprenolol (2 mg/kg) induced a highly significant decrease of mean arterial blood pressure and significant bradycardia. In the same model, the intravenous administration of saline, indomethacin, and clidanac did not affect the mean arterial blood pressure and heart rate. Pretreatment with indomethacin and clidanac reduced the effect of these beta-blockers on the mean arterial blood pressure and had no effect on the heart rate. Treating of the guinea pig heart homogenate with 1 microM indomethacin or clidanac decreased the number of beta-adrenoceptors without changing their affinity. These results suggest that indomethacin and clidanac interfere with beta-adrenoceptor-mediated effects.

Adrenergic beta-Antagonists↗
PubMed1983

[Opioid receptor interactions of butorphanol, a narcotic antagonist analgesic, and its metabolites].

The Opioid receptor affinities of butorphanol (BT) and its main metabolites, norbutorphanol (NB) and hydroxybutorphanol (HB), were determined by an in vitro receptor binding assay using crude synaptosomal membrane preparations of rat brain. BT showed high affinities to all types of the receptor except the alpha type (phencyclidine binding site), resulting in displacements of the bindings of mu (dihydromorphine)-, delta (D-Ala2-D-Leu5-enkephalin)- and kappa (ethylketocyclazocine)-ligands with more potency than morphine and ketocyclazocine, and it preferentially bound to mu- and kappa-opioid receptors. NB bound to the mu-binding site with affinity higher than that of pentazocine and to the kappa-binding site with the lowest affinity. HB exclusively bound to the mu-binding site with lower affinity. The affinities of BT, NB, HB and morphine to the alpha-site were smaller than those of pentazocine and ketocyclazocine. In the presence of 100 mM NaCl or by treating with 500 microM 5,5'-dithiobis (2-nitrobenzoic acid), the binding capacity of the membrane preparation was altered, and BT behaved as a typical antagonist. NB showed an agonistic property, and HB behaved as an antagonist. BT appears to be a mu-opioid receptor antagonist and has a kappa-receptor agonist-like character.

Animals↗
PubMed1983

[Correlation of biliary cholesterol, phospholipids and bile acid compositions and the development of cholesterol cholelithiasis in mice].

A study was attempted to establish a screening method for detecting cholelitholytic ingredients from a wide variety of natural substances. Although mice were selected as a suitable pathological model of cholelithiasis to detect a small amount of the ingredients, all the conventional lithogenic diets caused unfavorable influence on the animals. Therefore, as the first step we formulated a new lithogenic diet consisting of butter, cholesterol, cholic acid, etc, which was adequate for mice. Subsequently, the pathological characteristics and persistence of cholelithiasis were examined in the animals; the changes in bile compositions including free and conjugated bile acids, cholesterol and phospholipids were observed before and at the onset of cholelithiasis. Following confirmation of the stone formation, a normal diet was substituted for the lithogenic diet to likewise assess the bile compositions 4 and 6 weeks later. An increasing tendency for deoxycholic acid, disappearance of chenodeoxycholic acid and decrease in ursodeoxycholic acid were seen under the condition of cholelithiasis. In addition, the cholic acid-glycine conjugate which should not exist in the normal state and the increase in free and tauring-conjugated cholic acid were noticed. The biliary cholesterol level in treated mice increased to about 4 times higher than that in untreated mice, while the biliary phospholipids and total bile acids levels increased to only about 1.5 and about 2 times the control levels, respectively. The incidence of stone formation rose sharply at an experimental period between 2 and 3 weeks after starting the lithogenic diet. Gallstones die not disappear even at the 6th week after substituting a normal diet for the lithogenic one. However, the cholic acid-glycine conjugate disappeared, and deoxycholic acid as well as chenodeoxycholic acid and ursodeoxycholic acid tended to recover to the normal levels in the bile.

Animals↗
PubMed1983

[Physical dependence liabilities of butorphanol, a narcotic antagonist, and its main metabolites, norbutorphanol and hydroxybutorphanol].

After the intravenous injection of butorphanol or norbutorphanol in rats every 1 hr for 3 days, naloxone-induced body weight loss and withdrawal syndrome were observed to some degree. A slow-released emulsion containing each of the test drugs was injected subcutaneously in guinea-pigs, and naloxone was administered after 2 or 3 days. BT caused little jumping response even at a dose of 600 mg/kg, and the reaction was significantly weaker than that of pentazocine. No jumping responses were recognized in the cases of NB (600 mg/kg). In morphinized rats, the injection of BT or HB caused potent body weight loss, and these rats exhibited withdrawal syndrome which was more potent than that by pentazocine at the same dose. The body weight losses by the injection of NB and pentazocine were to the same degree, and these changes were significantly different from that of the saline control. BT inhibited the adenylate cyclase activity of the rat caudate nuclei, and the effect was weaker than that of pentazocine. NB showed a slight inhibition, and HB had no effect on the activity. These results suggest that the physical dependence liability of butorphanol is less than that of pentazocine, and the potent mu-antagonistic character of butorphanol is based on the liability. NB, a mu-agonist, makes dependence production possible. The ability of HB is negligible.

Animals↗
PubMed1983

Concurrent malignant lymphoma of the jejunum and multiple synchronous colon cancers.

This paper describes a unique case of combined malignant lymphoma of the jejunum and multiple synchronous carcinomas of colon and rectum. The jejunal tumor developed obstructive growth without regional lymph node involvement. Histologically, it was a malignant lymphoma corresponding to medium-sized cell type of follicular lymphoma, suggesting B cell origin in the bowel wall. In the colon and rectum, except for the transverse segment, there were three encircling, annular infiltrative tumors, and six polyps with malignant change. They developed independently, separated by an intact mucosa suggesting multiple synchronous cancers. Histologically they showed adenocarcinoma with or without mucus production, adenosquamous cell carcinoma, and villotubular adenocarcinoma. A case report is presented with a brief review of the incidence and pathogenesis of both jejunal and colonic tumors.

Adenocarcinoma↗
PubMed1982

Abnormal platelet aggregation response in Huntington's disease.

Platelet aggregation response to epinephrine, dopamine, serotonin, adenosine diphosphate, arachidonic acid, and collagen was examined in seven patients with Huntington's disease and nine of their relatives. All patients, except for two cases that were in terminal states, showed enhanced response to all the stimulants, especially to dopamine and epinephrine. The platelet aggregation response in many relatives also deviated from the normal limit. The relationship between platelet aggregation abnormality in Huntington's disease and the pathophysiology of the disease was discussed from the view of a generalized membrane defect hypothesis in Huntington's disease, and of disturbed cathecholamine metabolism, both in the CNS and periphery. A possibility that platelet aggregation response examination will be a useful screening test of offspring at risk was proposed.

Adenosine Diphosphate↗
PubMed1982

Biologically active principles of crude drugs. II. Anti-allergic principles in "Shoseiryu-To" anti-inflammatory properties of paeoniflorin and its derivatives.

Anti-inflammatory properties of paeoniflorin and its derivatives were examined in experimental animals. Paeoniflorin, desbenzoylpaeoniflorin and new monoterpene glucoside 'paeonon' inhibited experimental contact hypersensitivities and passive cutaneous anaphylaxis reaction. Paeonon inhibited tissue swelling in the adjuvant arthritis, while paeoniflorin and its related compounds were ineffective in inhibiting non-allergic inflammatory response.

Animals↗
PubMed1982

Elimination of GTP biphasic regulation of synaptosomal adenylate cyclase by manganese and solubilization.

Effects of divalent cations and solubilization with Lubrol-PX were studied on guanine nucleotide regulation of synaptosomal adenylate cyclase activity of the rat caudate nucleus. In the presence of Mg2+, both GTP and Gpp(NH)p exerted biphasic actions on the membrane-bound adenylate cyclase activity. The K0.5 value for the GTP stimulation of the cyclase was 47 nM, and the value for the GTP inhibition was 4.5 microM. One hundred microM dopamine selectively enhanced the stimulatory phase of the GTP action, whereas 10 microM morphine selectively enhanced the inhibitory phase of the GTP action. When Mg2+ was replaced by Mn2+, the inhibition of the membrane-bound adenylate cyclase by these nucleotides and morphine was completely abolished; but the catalytic activity of adenylate cyclase was not impaired. These results suggest that the inhibitory action of GTP is responsible for the morphine inhibition of synaptosomal adenylate cyclase. Lubrol-solubilized adenylate cyclase prefered Mn2+ to Mg2+ for its activity. The stimulation of adenylate cyclase by either GTP or Gpp (NH)p was eliminated in the Sepharose 6B-fractionated solubilized preparation in the presence of either Mg2+ or Mn2+. Ten mM NaF also failed to activate the fractionated adenylate cyclase. In the fractionated solubilized preparation, GTP and Gpp(NH)p failed to inhibit adenylate cyclase. These results indicate that GTP and Gpp(NH)p are unable to inhibit the resolved catalytic unit of the synaptosomal adenylate cyclase.

Adenylyl Cyclases↗
PubMed1982

[Cephem antibiotics and alcohol metabolism: (1) Disulfiram-like reaction resulting from intravenous administration of cephem antibiotics].

Fifty to 500 mg/kg doses of the cephem antibiotics were intravenously injected to male rats twice a day for 3 days. After the last injection, the rats were fasted for 17 hours and then orally administered 2 g/kg or 20% ethanol. The blood levels of ethanol and acetaldehyde (AcH) were determined by gas chromatography. Cefotiam, cefsulodin, and cefazolin did not affect the blood levels of ethanol and AcH as compared with those of the control. Cefmetazole, cefamandole, and cefoperazone did not change the blood ethanol level, but these antibiotics increased the blood AcH level dose-dependently. Cefamandole was especially able to sustain a high blood AcH level for over 8 hours. All of the antibodies which increased blood AcH levels contain the 1-methyl-1H tetrazole-5-thiol (TZ) group in their chemical structure. Intravenous injection of TZ caused a significant increase of the blood AcH level without influence on the blood ethanol level. 1-(2-Dimethyl-aminoethyl 1H-tetrazole-5-thiol (MTZ), the functional group which is contained in cefotiam, did not affect the blood levels of ethanol and AcH. These results suggested that the disulfiram-like reaction of cefmetazole, cefamandole, and cefoperazone results from an increase of the blood AcH level, and the 3-substituent group in in aminocephalosporanic acid, i.e., TZ, is an important factor for the reaction.

Acetaldehyde↗
PubMed1982

[Inhibitory effect of TN-762 (suprofen) on platelet aggregation].

Inhibitory effects of TN-762 (suprofen), ketoprofen, and indomethacin on rat or rabbit platelet aggregation were examined. Of these compounds tested, Suprofen showed the most potent effect on platelet aggregation in vitro, especially in AA-induced rabbit platelet aggregation (IC50 = 0.01 microM). Suprofen showed an inhibitory effect similar to that of ketoprofen and indomethacin on rat platelet aggregation ex vivo. The lethal effect of AA in the rabbits was protected by suprofen (0.05 mg/kg p.o.) at concentrations lower than the other compounds. Similar to the compounds, suprofen had little effect on the PG I2 synthesis in the rat aorta. In order to test the direct effects of these compounds on the platelet avoiding the effects of other plasma components, gel-filtrated rat platelets were used. All tested compounds showed similar inhibitory effect. To investigating the interaction of these compounds with the lipid bilayers, we used the liposome as a model membrane. The tested compounds inhibited liposome aggregation induced by 4 mM Ca2+. In this experiment, the interaction of suprofen with the lipid bilayers was shown.

Adenosine Diphosphate↗
PubMed1982

[Effect of tiemonium iodide on colonic motility in dogs].

Effects of tiemonium iodide (tiemonium, 20 micrograms/kg), mepenzolate bromide (mepenzolate, 20 micrograms/kg), butylscopolamine bromide (butylscopolamine, 50 micrograms/kg) and atropine sulfate (atropine, 10 micrograms/kg) on the colonic motility in dogs were evaluated using a balloon method. The frequency of the wave motion was analyzed by fast Fourier transform, and the power spectra were obtained. The value of the first term of the power spectrum is regarded as an indication of the colonic tonus. Inhibitory effects of tiemonium on both the normal proximal colonic motility and the accelerating motility induced by neostigmine metylsulfate (neostigmine, 50 micrograms/kg) were equal to those of butylscopolamine. In the case of distal colonic motility, tiemonium showed potent mepenzolate-like inhibition. When the drugs were injected into the veins after administration of PGF2 alpha (10 micrograms/kg), all of the drugs depressed the colonic constriction induced by PGF2 alpha. The colonic motility was not restored by the administration of tiemonium or mepenzolate before the injection of PGF2 alpha, but such an effect was not observed in the case of butylscopolamine and atropine. It is suggested that tiemonium shows an extensive inhibition on the colonic motility in the mode of mepenzolate-like action and by some additional mechanism.

Animals↗
PubMed1982

[Anti-inflammatory, analgesic and antipyretic activities of alpha-(p-thenoylphenyl)-propionic acid (TN-762) (author's transl)].

We reported in our previous paper that TN-762, a potent inhibitor of prostaglandin biosynthesis, has marked inhibitory activity on acute experimental inflammation. In this paper, the anti-inflammatory, analgesic, and antipyretic activities of TN-762 were assessed in animal models, and compared with those of indomethacin, ketoprofen and ibuprofen. TN-762 inhibited the sustained paw edema induced by mustard in rats during administration for 3 days, but after final administration, the inhibitory activity was decreased rapidly and was less then that of ketoprofen and indomethacin. TN-762 also inhibited the proliferation of granuloma induced by means of cotton pellet and granuloma pouch methods, and the adjuvant arthritis in rats. The inhibitory activity of the compound on inflammatory proliferation was more potent than that of ibuprofen, but slightly less than that of ketoprofen and less than about 1/10 times that of indomethacin. Indomethacin markedly inhibited the body weight gain at a high dose, while TN-762 did not affect it. Therefore, TN-762 was proven to have an inhibitory effect on subacute and chronic inflammation at low doses without toxic effects, but the compound appeared to have a less of an inhibitory effect on secondary or late stages of inflammation than on primary stage inflammation. TN-762 inhibited the acute paw edema induced by nystatin, and the inhibitory activity was the same as that of ketoprofen and indomethacin. The pathogenesis of nystatin edema has been considered to be due to lysosomal labilization. This result suggests that TN-762 has a potent membrane stabilizing action which is considered to be one of the necessary mechanisms in anti-inflammatory action. On the other hand, TN-762 showed the same potent analgesic effect as ketoprofen and indomethacin as observed by the acetic acid writhing and modified Haffner's methods in mice and by the Randall-Selitto's method in rats. However the antipyretic effect of TN-762 was significantly less than that of ketoprofen and indomethacin.

Analgesics↗