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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 1,045 records · Page 58Linked to original sources

Effects of azelastine on allergen- and exercise-induced asthma.

The effects of the new anti-allergic drug, azelastine, on allergen- and exercise-induced asthma were studied. In six allergen inhalation tests for five asymptomatic asthmatic patients, the maximum percentage fall in FEV1.0 immediately after inhalation of allergen extract was 37.2 +/- 6.4 per cent (mean +/- SEM). As compared with a placebo, the maximum percentage fall in FEV1.0 with azelastine after inhalation of allergen extract in the same manner as with the placebo was 17.3 +/- 6.9 per cent. The difference was statistically significant (p less than 0.05). The percentage fall in FEV1.0 with placebo and azelastine in late asthmatic response (n = 4) was 36.0 +/- 5.3 per cent and 10.0 +/- 5.2 per cent, respectively. The difference was also statistically significant (p less than 0.01). An exercise test was carried out on seven asymptomatic asthmatic patients using an inclined treadmill. The maximum percentage fall in FEV1.0 without drugs, with diphenhydramine and azelastine was 38.9 +/- 5.0 per cent, 20.1 +/- 3.8 per cent and 11.3 +/- 3.1 per cent, respectively. Significant differences were found among each group (p less than 0.05). Azelastine was regarded as having sufficient potency to inhibit exercise-induced asthma; however, placebo effects cannot be ruled out with regard to the effects of diphenhydramine. These results suggests that chemical mediator release is involved not only in allergen-induced asthma but also in exercise-induced asthma, suggesting the clinical utility of azelastine.

Adolescent↗

Calcium ionophore A23187 calcium-dependent cytolytic degranulation in human eosinophils.

The divalent cation ionophore A23187 is frequently used for studies of eosinophil degranulation. Nonetheless, the mechanism whereby A23187 induces degranulation in human eosinophils is still unclear. In the present experiments, A23187 caused human eosinophils to release a granule protein, eosinophil-derived neurotoxin (EDN) and a membrane-associated protein, Charcot-Leyden crystal (CLC) protein in a calcium and a concentration-dependent manner. However, A23187 at a concentration (1 microgram/ml) that caused 15% EDN release and 30% CLC protein release also produced release of the cytoplasmic enzyme lactic dehydrogenase (LDH) and loss of cell viability, both of which were calcium dependent. CLC protein release preceded EDN release and was detectable even at 15 min after the addition of 1 microgram/ml A23187, whereas EDN release occurred after a lag period of 30 min, and coincided with LDH release. At 1 microgram/ml A23187, neither the release of LDH nor the loss of viability occurred with purified neutrophils obtained in the same blood sample as a by-product of eosinophil purification. Electron microscopic examination demonstrated that exposure to A23187 for 15 min resulted in an increase and elongation of microridges on the cell surface, and exposure for 45 min caused cell disruption followed by extrusion of membrane-bound granules through breaks in the plasma membrane. Only once was granule exocytosis observed. These results indicate that A23187 treatment of eosinophils causes an initial release of membrane-associated CLC protein by a noncytolytic mechanism, and causes degranulation as a result of eosinophil lysis.

Blood Proteins↗

[Fundamental and clinical studies on cefminox in the field of obstetrics and gynecology].

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied both fundamentally and clinically with following results. In 33 cases undergone total hysterectomy and adnexectomy, 1 g of CMNX was administered intravenously by the drip infusion route over 1 hour and changes in drug concentration in the venous blood and uterine arterial blood as well as in various uterine tissues including endometrium, myometrium, cervix uteri, portio vaginalis, oviduct and ovary were studied. In addition, in 3 cases also received 1 g of CMNX over 1 hour by the drip infusion route, changes in the concentration of CMNX in the pelvic dead space exudate were investigated. In each tissue studied, the drug concentration higher than 40 micrograms/g was attained at 20 minutes after completion of drip infusion, showing good transfer of CMNX. In the pelvic dead space exudate, the peak concentration of 24.7 micrograms/ml appeared at 4 hours after completion of drip infusion and at 12 hours still a concentration of 4.5 micrograms/ml was maintained. In the treatment of 15 cases of obstetrical and gynecological infections, CMNX was used. In all of the cases treated, clinical results better than good were obtained, with excellent results in 2 cases and good results in 13 cases. In none of the cases side effects or laboratory abnormalities were observed. From these results CMNX is considered to be a useful drug for the treatment of various infections in the field of obstetrics and gynecology.

Adnexa Uteri↗

Reduced taurine contents and modification of anticonvulsive effects of phenobarbital and phenytoin by guanidinoethane sulfonate in mice.

In the present study, we investigated whether administration of guanidinoethane sulfonate, and inhibitor of taurine uptake, worsens electroshock-induced convulsions or modifies the antiepileptic actions of phenobarbital or phenytoin against maximal electroshock seizures in mice. Treatment with 1% guanidinoethane sulfonate in drinking water for 9 days decreased taurine concentration in the brain to 76% of control value. Under these conditions, neither the severity of tonic convulsions of maximal electroshock seizures nor the threshold for tonic extension caused by electroshock was altered. On the other hand, the antiepileptic potency of phenobarbital and phenytoin against tonic convulsions of maximal electroshock seizures in mice was significantly lessened by chronic administration of guanidinoethane sulfonate. This decrease in potency was not due to an alteration in pharmacokinetics, as the brain levels of these drugs were unchanged. Furthermore, administration of the anticonvulsive drugs did not change brain concentrations of guanidinoethane sulfonate and total guanidino compounds. It is suggested that the observed loss of anticonvulsive potency of phenobarbital and phenytoin may be related to the decreased concentration of taurine produced by administration of guanidinoethane sulfonate.

Amino Acids↗

[Clinical studies on cefpiramide].

A new cephalosporin, cefpiramide was administered to 12 patients with gynecological infections and the clinical effects obtained were good in 11 cases and poor in 1 (effective ratio: 91.7%). No side effects were observed except for eruption in 1 case, however, the relationship between the drug and eruption was unknown. No abnormalities were observed in hematological, hepatic and renal tests.

Adult↗

Sensitive enzyme immunoassay for the measurement of platelet factor 4 in blood plasma.

A sandwich enzyme immunoassay method for the measurement of platelet factor 4 (PF4) was developed with the use of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from E. coli. The measurable range was 30 pg to 3 ng of PF4 per tube. Within-run and between-run coefficients of variation were less than 10%. The results obtained with the enzyme immunoassay correlated well with those of a radioimmunoassay (r = 0.952, slope = 0.954, gamma-intercept = 2.43 ng/ml). Platelets contained large amounts of PF4 (7.21 +/- 1.97 ng/10(6) cells or 2.51 +/- 1.13 ng/mg protein), whereas the PF4 levels in red blood cells and lymphocytes were negligible, confirming the specific localization of PF4 in platelets. The applicability of the immunoassay method was tested to determine the in vitro release of PF4 during preparation and storage of platelet concentrates.

Adult↗

Corneal lesions induced by the systemic administration of capsaicin in neonatal mice and rats.

Following a single subcutaneous injection of capsaicin to neonatal mice, a high incidence of corneal lesions with opacity developed after a long latency. The intensity of the lesions progressed for about 1 month in animals which had received a high dose (50 or 100 mg/kg) of capsaicin. Although the intensity gradually decreased thereafter, 50% of animals still exhibited a visible opacity 6 months after treatment. Similar corneal lesions were also produced in neonatal rats which had been injected with capsaicin. It is suggested that the corneal lesions induced by capsaicin may be due to destruction of the trigeminal nerve.

Aging↗

Capsaicin-induced neuroparalytic keratitis-like corneal changes in the mouse.

A single subcutaneous injection of 12.5-100 mg kg-1 capsaicin to newborn mice produced gross corneal changes. The changes were manifest about three weeks after capsaicin treatment and progressed dose-dependently from slight punctate vesiculations in the epithelium to diffuse edematous opacities and vascularizations in the stroma, followed by recovery in several weeks with or without residual scars. Control newborn mice with vehicle solution did not show any corneal abnormality. The most prominent histopathological feature of the affected corneas was a marked loss of nerve axons in the epithelium with associated disorganization of the epithelium. Similar corneal changes were observed with systemic capsaicin treatment to young or adult mice. The pathogenesis of the capsaicin-induced corneal changes was discussed with reference to the trophic action of the trigeminal nerve.

Animals↗