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Biomedical subjects

Y Osada

Publications and source records attributed to Y Osada.

At least 163 records · Page 9Linked to original sources

In vitro activity of DQ-2556, a new cephalosporin.

The in vitro antibacterial activity of DQ-2556, a new semisynthetic cephalosporin, was compared with that of ceftazidime and cefotaxime. The activity of DQ-2556 against members of the family Enterobacteriaceae was roughly comparable to that of cefotaxime. Against Pseudomonas aeruginosa, DQ-2556 was slightly less active than ceftazidime. DQ-2556 was more active than the reference cephalosporins against staphylococci. Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DQ-2556.

Bacteria↗

Chemotherapeutic efficacy of ofloxacin on renal and subcutaneous infection models with Staphylococcus aureus in mice.

Ofloxacin, a new pyridone-carboxylic acid derivative, was evaluated in descending nephritis and subcutaneous abscess models with Staphylococcus aureus in mice in comparison with norfloxacin. Descending nephritis was produced by intravenous injection of S. aureus 39 (MIC 0.78 microgram/ml for ofloxacin and 3.13 micrograms/ml for norfloxacin). Subcutaneous abscess was established by subcutaneous injection of soft agar containing S. aureus 56230 (MIC 0.39 microgram/ml for ofloxacin and 1.56 micrograms/ml for norfloxacin). Three days after infection, the lesions of both models were characterized by purulent inflammation accompanied with massive infiltration of neutrophils and bacterial multiplication. The animals were treated twice a day orally with each compound for 4 consecutive days, and subjected to bacteriological examination 18 h later. In the renal model, the 50% effective doses calculated on the basis of clearance of bacteria from kidneys were 38.4 mg/kg for ofloxacin and greater than 100 mg/kg for norfloxacin. In the subcutaneous model, the 50% effective doses based upon 90% reduction of viable bacteria as compared with untreated controls were 25.2 mg/kg for ofloxacin and greater than 100 mg/kg for norfloxacin. The excellent efficacies of ofloxacin in both infection models are attributed to its high oral absorbability and tissue distribution.

Abscess↗

Augmentation by bacterial lipopolysaccharide of antitumor potency of murine recombinant interferon-gamma against Lewis lung adenocarcinoma.

Stimulation by recombinant murine interferon-gamma (rMuIFN-gamma) of host defenses against the growth of Lewis lung adenocarcinoma, cell line 3LL, in the lung was examined. 3LL cells were resistant to in vitro antiproliferative activities of rMuIFN-gamma. On the other hand, rMuIFN-gamma augmented the killer activities of the non-adherent population of spleen cells and peripheral blood mononuclear cells (PBMC) in vivo, and the IFN also stimulated the cytostatic activities of peritoneal and splenic macrophages, but not alveolar macrophages. The combination of rMuIFN-gamma with LPS synergistically activated macrophages from the lung, as well as the peritoneal cavity and the spleen, to become both cytostatic and cytolytic against 3LL cells. The macrophages activated in vitro by simultaneous incubation with these agents markedly suppressed the growth of 3LL cells in vivo. The growth in the lung of 3LL cells implanted iv was significantly (P less than 0.05) suppressed by combination therapy with rMuIFN-gamma and LPS, but not by either agent alone. These results indicate that the potency of rMuIFN-gamma action against 3LL cells can be augmented by combination with LPS, mainly through synergistic macrophage activation.

Adenocarcinoma↗

Binding of human gamma-interferon to human epidermal tumor cells with different susceptibilities.

The in vitro antiproliferative effect of highly purified recombinant human gamma-interferon was studied with special reference to specific binding to tumor cells of interferon (IFN) labeled with 125I. Recombinant human gamma-interferon markedly suppressed the growth of 6 of 10 human epidermal tumor cell lines tested; the concentration required to inhibit the growth of susceptible cell lines by 50% ranged from 8 to 36 units/ml (13.6 to 61.2 pM), whereas those for the other cell lines were higher than 10,000 units/ml. These anticellular effects were compatible with the suppressive effects of IFN on cellular DNA synthesis. Labeled IFN bound specifically to the susceptible cells, which showed, from the Scatchard analysis, 870 to 7700 binding sites/cell with apparent Kd of 1.70 to 5.84 X 10(-11) M. There was little binding of the labeled IFN to the resistant cells and nonspecific binding occurring in the presence of a 1000-fold excess of unlabeled IFN accounted for 40 to 90% of the total binding. These results suggest that specific binding sites for recombinant human gamma-interferon exist on the resistant cell lines.

Cell Cycle↗

In vitro and in vivo activities of DN-9550, a new broad-spectrum cephalosporin.

DN-9550 [(6R, 7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1H-imidazol-4-yl) methoxyiminoacetamido]-3-[(1-pyridinio)methyl]-8-oxo-5-thia -1-azabicyclo methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrochloride] is a new semisynthetic cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. The activity of DN-9550 against most species of the family Enterobacteriaceae was roughly comparable to that of ceftazidime, slightly lower than that of cefotaxime, and far exceeded that of cefoperazone. Against Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens, DN-9550 was more active than ceftazidime and cefotaxime. DN-9550 and ceftazidime were significantly more active than cefotaxime against Pseudomonas aeruginosa, but DN-9550 and cefotaxime were clearly more active than ceftazidime against staphylococci and streptococci. Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DN-9550, but Bacteroides fragilis was generally not susceptible to the compound. DN-9550 was stable to various types of beta-lactamases and had high affinities for penicillin-binding protein 3 of both Escherichia coli and P. aeruginosa. When DN-9550 was administered subcutaneously to mice experimentally infected with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, or Pseudomonas aeruginosa, its efficacy well reflected its in vitro potency.

Animals↗

Stimulation by staphylococcal enterotoxin A of nonspecific resistance of mice to microbial infection.

The effects of staphylococcal enterotoxins A, B, and C2 (SEA, SEB, and SEC2) on the resistance of mice to microbial infections were studied. SEA stimulated the resistance strongly, whereas SEB and SEC2 had no such effect. Treatment with SEA increased the number of peripheral blood polymorphonuclear leukocytes significantly within 4 h, and these polymorphonuclear leukocytes exhibited a higher chemiluminescence response than those of the controls. Furthermore, a significant increase in spleen weight was also observed in mice treated with SEA, and histologically that increase was characterized by a proliferation of lymphoblast-like cells which were stained with antibody to mouse Thy-1 but not with antibody to mouse immunoglobulin G by indirect immunofluorescence. As expected from the above findings, the treatment of nude mice (nu/nu) with SEA failed to protect them against Escherichia coli infections, whereas treatment of heterozygous (nu/+) controls afforded such protection. This was in part supported by the fact that the chemiluminescence response of peripheral blood polymorphonuclear leukocytes was increased significantly by treatment with SEA in nu/+mice but not in nu/nu mice.

Animals↗

Adverse effects during endocrine therapy for prostatic carcinoma with a high dose of estrogen.

A clinical study of the adverse effects induced by the endocrine therapy with a high dose of estrogen in 45 patients with stage C or D prostatic carcinoma is conducted. Transient decreases of hemoglobin and serum protein values were observed after administration of estrogen. The levels of glutamine-oxaloacetic and glutamic-pyruvic transaminase showed a transient increase. The value of serum total cholesterol and electrolytes showed no changes. Serial evaluations of electrocardiograms have played a minor role in the observation of cardiovascular disease. Up to date we have not experienced cardiovascular death in our cases during the endocrine therapy.

Aged↗

Simultaneous bilateral testicular torsion in the adolescent.

A rare case of simultaneous bilateral testicular torsion in a 12-year-old boy is reported. Although an acute scrotal emergency of unilateral testicular torsion is not uncommon, bilateral testicular torsion, synchronous or asynchronous, is rare.

Child↗

[The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid].

The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid were investigated using some experimental animal models. Anti-inflammatory potencies of aspirin were almost equal to those of sodium salicylate in the carrageenin hind paw edema, the cotton pellet granuloma and the adjuvant arthritis tests in rats. On the other hand, in the ultra-violet ray erythema and the arachidonic acid erythema tests in guinea pigs, aspirin was more potent than sodium salicylate. Aspirin and sodium salicylate exhibited almost the same inhibitions of the rat hind paw edema induced by a mixture of carrageenin and prostaglandin E1. These results suggest that inhibition of cyclo-oxygenase by aspirin does not play any important roles for the prevention of the vascular permeability increment and the granulation in the inflamed tissue. Aspirin may exert its antiinflammatory activity mainly as salicylic acid which is not an inhibitor of prostaglandins biosynthesis in vitro. Aspirin showed about 5 times more potent analgesic action than sodium salicylate in the lameness test using adjuvant arthritic rats. Analgesic potency of aspirin was decreased to the level of sodium salicylate by injection of prostaglandin E2 into the inflamed rat paw in the adjuvant-induced lameness test. On the other hand, analgesic potency of sodium salicylate was not decreased by the same treatment. It is concluded that aspirin has two analgesic effects on the inflammatory pain, one is inhibition of prostaglandins biosynthesis by acetylation of cyclo-oxygenase and the other is an action due to salicylic acid, but the action of salicylic acid was not totally explained by the inhibition of prostaglandins synthetase.

Animals↗

Effect of albumin immobilization by plasma polymerization on platelet reactivity.

Albumin was immobilized on polyethylene (PE) film by the plasma polymerization method. Immobilized albumin on formaldehyde polyermized PE film was hard to desorb even when the film was dipped in blood plasma. Amounts of platelet adhesion on the film and serotonin release decreased clearly. Aggregated platelets were observed on PE film but not observed on the albumin immobilized surface. These results seemed to be due to not only immobilized albumin, but also the surface charge determined by plasma protein adsorption. That is, the slightly negatively charged surface indicated good anti-thrombogenicity.

Albumins↗

Outbreak of nosocomial urinary tract infections caused by Serratia marcescens.

A prolonged outbreak (December 1980 to July 1982) of nosocomial urinary tract infections appeared to be due to strains of Serratia marcescens that were resistant to currently available antibiotics. The serotyping and antibiotic susceptibility patterns suggested a few endemic strains of serotypes O13, O2/3, O12/14, and nontypable strains. These strains were isolated from the urine samples of inpatients with urinary tract infections in the urology ward and in other wards. The strains of O12/14 (gentamicin susceptible) were replaced with those of O2/3 (gentamicin resistant) between June and September 1981, whereas the other serotypes were isolated continuously. They were resistant to sulbenicillin, cefmetazole, gentamicin, and amikacin, and susceptible to micronomicin and of loxacin, a new quinolone antibiotic. Most of them were also resistant to the disinfectant chlorhexidine, which had been used widely for hand washing in the hospital.

Anti-Bacterial Agents↗

[Anti-inflammatory activity of a non-steroidal anti-inflammatory agent, oxaprozin, in experimental models].

Anti-inflammatory activity and mode of action of oxaprozin, a new non-steroidal anti-inflammatory agent, were investigated in experimental animal models and in vitro tests. Anti-inflammatory potency of oxaprozin was almost equal to that of aspirin in acetic acid vascular permeability, carrageenin hind paw edema, cotton pellet granuloma and adjuvant arthritis tests in rats. On the other hand, in mice, oxaprozin was more potent than aspirin, ibuprofen and phenylbutazone, and it was as potent as sulindac and fenbufen in acetic acid vascular permeability and carrageenin hind paw edema tests. In adrenalectomized rats, the anti-edema activity of oxaprozin in the carrageenin hind paw edema test was the same as that in intact rats. Oxaprozin inhibited erythema formation induced by ultra-violet rays in guinea pigs. The inhibitory potency of oxaprozin against prostaglandin E2 biosynthesis in vitro was equal to that of ibuprofen. Oxaprozin showed a concentration-dependent inhibition of heat-induced denaturation of bovine serum albumin and lysis of rabbit erythrocytes in vitro. However, oxaprozin did not inhibit rat hind paw edemas induced by dextran, formalin and serotonin. It was suggested from these results that the mode of action of oxaprozin is similar to those of other acidic non-steroidal anti-inflammatory drugs. Ulcerogenicity of oxaprozin was weaker than those of phenylbutazone and aspirin in rats. Species differences in the metabolic rate of oxaprozin were shown. The blood concentration of oxaprozin in rats is extremely low because the metabolic rate of oxaprozin is rapid in rats. Therefore, in rats, oxaprozin exhibited a weak anti-inflammatory effect. However, in mice, oxaprozin had a low metabolic rate, and the effect of oxaprozin was as potent as sulindac and fenbufen. The elimination half-life of oxaprozin is extended, 49 to 69 hr, in humans. It was suggested from these findings that oxaprozin is a potent and long acting anti-inflammatory drug in clinical use.

Animals↗

[Effects of anti-inflammatory drugs on the lame walking reaction in adjuvant-induced edematous rats].

Acute inflammatory paw edema of rats was formed by the injection of 0.5% Mycobacterium tuberculosis-liquid parraffin suspension into the hind paw, and then the pain threshold of the inflamed paw decreased. At that time, the rats showed a three-legged gait, namely, the lame walking reaction. The reaction was inhibited by acidic nonsteroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and aspirin, inhibitors of prostaglandins biosynthesis, at a lower dose level than those in the Randall-Selitto test using yeast edematous rats and in the flection tests using adjuvant arthritic or silver nitrate arthritic rats. On the other hand, basic nonsteroidal anti-inflammatory drugs, e.g., tiaramide HC1, mepirizole and perisoxal citrate, not inhibitors of prostaglandins biosynthesis, were less potent than the acidic nonsteroidal anti-inflammatory drugs in the inhibition of the lame walking reaction. When prostaglandin E2 was injected into the inflamed paw, the inhibitory effects of acidic non-steroidal anti-inflammatory drugs on the reaction disappeared, but those of the basic nonsteroidal anti-inflammatory drugs didn't disappear. Bradykinin had no influence on the effects of both acidic and basic nonsteroidal anti-inflammatory drugs in the inhibition of the reaction. Analgesic evaluation with the lame walking reaction is more sensitive than with the Randall-Selitto or the flection methods. Morphine, pentazocine and acetaminophen inhibited the reaction, and these effects didn't disappear by the injection of prostaglandin E2 into the inflamed paw. These results suggest that prostaglandins play important roles in inflammatory pain, and the lameness test can serve as a new method for evaluating analgesics such as anti-inflammatory drugs and for investigating the mechanism of inflammatory pain.

Analgesics↗