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Biomedical subjects

H Fujimura

Publications and source records attributed to H Fujimura.

At least 127 records · Page 7Linked to original sources
PubMed1984

[The effects of various drugs on the binding site of bilirubin in serum albumin].

In the presence of various drugs, the concentration of free bilirubin which was released from the first binding site of bilirubin in serum albumin was evaluated, using a sensitive method based on static fluorescence quenching of dansyl serum albumin. Bilirubin bound to human serum albumin more strongly than to bovine serum albumin. Non-steroidal anti-inflammatory drugs, fenamates and allylphenyl propionic acids, affected the bilirubin-serum albumin interaction. Flufenamic acid and ketoprofen released bilirubin from human serum albumin. The bilirubin bound to the serum albumin was not influenced by the presence of indomethacin, but clidanac strongly dissociated bilirubin from the bilirubin-serum albumin complex. Sulfa-drugs, antibiotics, steroidal agents, warfarine, tolubutamide and phenytoin showed no significant effects on the bilirubin-serum albumin interaction. The fluorescence quenching method may be useful to evaluate the interaction of drug-bilirubin-serum albumin.

Animals↗
PubMed1984

[Interaction of suprofen and serum albumin].

The serum albumin-interaction of suprofen (SPF), a novel anti-inflammatory drug, was compared with those of indomethacin (IM) and ketoprofen (KTP). The binding constants of these drugs were determined with difference absorption spectra based on the binding to bovine serum albumin (BSA). The constants for SPF and IM were nearly equal, and the value for KTP was smaller than those of the other drugs. The magnitude of the inhibitory effect on heat denaturation of BSA reflected the difference in these binding constants. In the presence of these drugs, the tryptophan fluorescence in BSA was quenched (IM, SPF and KTP, in this order). The metachromagy based on the binding of an azodye, HABA, to BSA was potentiated by IM or SPF. Phenylbutazone suppressed the absorption of the metachromagy. SPF displaced only the binding of the fluorescent Site II probe, dansylproline, to human serum albumin (HSA), and both the bindings of dansylproline and dansylamide (Site I probe) to HSA were inhibited by KTP or IM. KTP released bilirubin from BSA and HSA, but SPF and IM did not show any effects on the bilirubin-serum albumin binding. These results all support that there is considerable interaction between SPF and serum albumin and that the mode of the interaction differs from those of KTP and phenylbutazone.

Animals↗
PubMed1984

[Active oxygen and anti-inflammatory drug: measurement by luminol dependent chemiluminescence].

The active oxygen produced from stimulated phagocytic cells emits luminol-dependent chemiluminescence (CL) upon reaction with luminol. So the active oxygen was measured by using the CL and the results of this were compared with those by the LDH-NADH method. Moreover, effects of nonsteroidal anti-inflammatory drugs (NSAID) on the generation of active oxygen were studied by both methods. Rat peritoneal and pleural exudated cells (PEEC and PLEC) emitted strong CL on incubation with zymosan, but that from rat whole blood cells was very weak. The effects of superoxide dismutase, catalase, NaN3 and L-ascorbic acid on the generation of active oxygen from rat phagocytic cells were different between CL and LDH-NADH methods. These discrepancies seem to be due to the different kinds of active oxygen that can be measured by both methods. Except for BW-755C, most of the NSAID had only a slight inhibitory effect on the generation of active oxygen measured by both methods, and the ex vivo effect was the same as that observed in vitro. It may be considered that NSAID decrease the phagocytic function of cells by non-specifically stabilizing the biological membrane and inhibit slightly the generation of active oxygen from phagocytes. On the other hand, the CL method could be performed not only in PEEC and PLEC, but also in whole blood cells. From these results, it was suggested that CL measurement can be used as a simple and valuable method for the detection of all types of active oxygen including superoxide anion radical and its metabolites and for testing cellular functions and drug actions on them.

Animals↗
PubMed1983

Regulation of opioid receptor binding; possible mechanisms of sulfhydryl groups in the binding site.

Opioid receptor bindings of four different ligands, dihydromorphine (DHM), D-Ala2-D-Leu5-enkephalin (DADLE), ethylketocyclazocine (EKC) and phencyclidine (PCP), were investigated with the treatment of 5,5'-dithiobis-(2-nitrobenzoic acid), DTNB, and 5,5'-dithiobis-(2-nitro-N-2'-hydroxyethylbenzamide), DTNHEB; a relative positive charged analog of DTNB. DTNB and DTNHEB effectively inhibited the binding of DHM and DADLE. Despite the presence of maximally effective concentrations of DTNB for DHM and DADLE, the receptor binding of EKC decreased intermediately, like effect of a partial agonist. DTNHEB inactivated the binding of EKC in a similar fashion to that of DHM. DTNB did not alter the intensity of the decrease of EKC binding by DTNHEB, even given concurrently. It suggests that an anionic center of the receptor has multiple active sulfhydryl sites. The ability of GTP to inhibit DADLE binding to the receptor disappeared by the pre-treatment of DTNB, and DTNB-induced inactivation of opioid agonist binding was potentiated in the presence of NaCl. DTNB-sensitive site may couple a mechanism of ligand binding that GTP regulated. The receptor binding of PCP was not influenced by DTNB and/or DTNHEB.

Animals↗
PubMed1983

(1,2-Diphenylethyl) piperazines as potent opiate-like analgesics; the unusual relationships between stereoselectivity and affinity to opioid receptor.

A series of novel diphenylethylpiperazines were synthesized, and analgesic activities and opioid receptor interactions were evaluated. Analgesic activity of S(+) enantiomer of 1-cyclohexyl analogues (I-C6) was as potent as morphine. This compound showed narcotic properties. Racemate of I-C6 demonstrated the most potent analgesic activities among the enantiomorphic pairs. The R(-) isomer and (-) spa, NN-dimethyl-1, 2-diphenylethylamine, had mu-agonist like character. The S(+) isomer possessed high affinity for all types of the receptor, especially favorable for delta and kappa, in the different manner from opiate-like analgesics. It is conceivable that opioid receptor has various subsites, and this S(+) enantiomer alter the conformation of the receptor.

Analgesia↗
PubMed1983

Platelet aggregation response in schizophrenia and prostaglandin E1.

Platelet aggregation response to various stimulants was examined in 18 unmedicated schizophrenic patients, 13 medicated patients, and 13 control subjects. Platelet aggregation response to epinephrine decreased only in unmedicated schizophrenic patients. Clinical improvement in seven patients after neuroleptic medication was significantly correlated with an increase in platelet aggregation response to arachidonic acid, and nonsignificantly to epinephrine, dopamine, and serotonin. The inhibitory effect of prostaglandin E1 on platelet aggregation response to adenosine diphosphate was investigated in seven unmedicated schizophrenic patients, six medicated patients, and eight controls. The inhibitory effect of prostaglandin E1 on platelet aggregation response to adenosine diphosphate was significantly reduced in all unmedicated schizophrenic patients. Neuroleptic medication had some effect in normalizing aberrant sensitivity to prostaglandin E1 in those patients, although acute medication induced an adverse reaction in the controls.

Adenosine Diphosphate↗
PubMed1983

Anti-inflammatory effect of diclofenac-sodium ointment (cream) in topical application.

This study was performed to develop a topical ointment of diclofenac-Na which has a potent anti-inflammatory activity by oral administration. At first, research was carried out on the ointment base which influences the external anti-inflammatory effect of the drug. Ointments of diclofenac-Na were prepared with three kinds of bases: lipophilic, emulsion (cream) and gel bases; and their anti-inflammatory effects were compared. The cream was found to have the most potent effect. Therefore, in the next experiment, an optimum concentration of diclofenac-Na in cream was determined comparing the anti-inflammatory effect among the cream preparations containing 0.5, 0.75, 1.0 and 1.5% of the drug. Obvious effects were observed with the cream containing 1.0% and 1.5% of the drug concentration, and there was no significant difference in the anti-inflammatory activities of these two concentrations. Based on these results, the cream preparation containing 1.0% of diclofenac-Na (DF cream) was adopted as the external ointment of the drug. The anti-inflammatory effect of this cream was compared with that of existing anti-inflammatory ointments, i.e., indomethacin gel (IM gel), bufexamac cream (BM cream) and mobilat ointment (ML ointment). DF cream produced obvious inhibition on increased vascular permeability and on acute edema and remarkable suppression of ultraviolet erythema. These activities of DF cream were similar to those of IM gel and more potent than those of BM cream and ML ointment. The inhibitory effect of DF cream on the proliferation of granulation tissue was almost equal to that of ML ointment and more distinguishable than that of IM gel and BM cream. In adjuvant arthritis, DF cream reduced the swelling remarkably in the treated paw and slightly in the untreated paw. The anti-adjuvant activity of DF cream was equal to that of IM gel and more potent than that of BM cream and ML ointment. In pain to pressure stimulation, an analgesic effect was observed in the early stage of DF cream application, and its activity was slightly stronger than that of the other ointments. These results show that DF cream has an obvious anti-inflammatory effect as an external preparation, and the activity is comparable or superior to that of similar existing anti-inflammatory ointments. This cream may be considered as useful in the clinical field as a topical anti-inflammatory preparation.

Administration, Topical↗
PubMed1983

Effect of anti-inflammatory drugs on endotoxin-induced diarrhea in mice.

Prostaglandins (PGs) increase the intestinal fluid to result in diarrhea. Some laxatives are known to exert their actions partially by stimulating the PGs biosynthesis. On the other hand, it is well documented that nonsteroidal anti-inflammatory drugs (NSAID) inhibit markedly the PGs biosynthesis. Since endotoxin (ETX) also produces diarrhea similarly in all species of experimental animals, we investigated the effect of various NSAID and steroidal anti-inflammatory drugs (SAID) on ETX-induced diarrhea in mice. ETX given p.o. did not produce diarrhea, but it could induce it after parenteral administration, especially intravenous injection. ALL NSAID and SAID tested inhibited ETX-induced diarrhea at dose levels similar to or lower than those commonly producing an acute anti-inflammatory effect. The anti-diarrheal effects were found in not only acidic NSAID, but also in basic NSAID and SAID which did not inhibited ultraviolet erythema, acute death induced by arachidonic acid injection and PGs biosynthesis. Therefore, this test using ETX-induced diarrhea in mice may be used as a new and desirable method for screening or evaluating anti-inflammatory drugs. The mechanism of diarrheogenic action of ETX is poorly understood, but may be attributed to inhibition of PGs biosynthesis besides other unknown actions.

Animals↗
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↗