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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 937 records · Page 52Linked to original sources
PubMed1986

Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs.

When rat mast cells loaded with fluorescent Ca2+ indicator Quin 2 were exposed to either compound 48/80 (0.1 micrograms/mL) or substance P (2 microM) at 37 degrees C for 30 seconds in a Ca-free medium, a marked increase of Quin 2 fluorescence was noticed, indicating that Ca2+ was released from the intracellular Ca store. The pixel values of the whole cell image were displayed in a three dimensional projection. When mast cells were exposed to 48/80, the fluorescent increase was reflected as an increase of height and spreading of the image. When 0.01 to 1 mM of db-cAMP was pretreated for five minutes, an increase of Quin 2 fluorescence was inhibited in a dose-dependent fashion. Theophylline pretreatment also showed a preventive effect at 1 to 5 mM. A marked inhibition of the Quin 2 signal was induced by pretreatment with 0.01 mM of terfenadine (63.4% inhibition) or ketotifen (26.6% inhibition). Disodium cromoglycate also showed a similar inhibitory effect. In the measurement of the order parameters of liposomes, the addition of either terfenadine or ketotifen into the lipids increased the parameter value, indicating they provide the membrane stabilizing action.

Aminoquinolines↗
PubMed1986

[Echo and Doppler cardiographic findings of isolated quadricuspid aortic valve: a case report and a review of the literature].

The two-dimensional and pulsed Doppler echocardiographic features of a case of isolated quadricuspid aortic valve with aortic regurgitation are described. A 62-year-old woman was hospitalized for exertional palpitation and dyspnea. Her physical examination showed the typical findings of aortic regurgitation. Two-dimensional echocardiograms revealed the aortic valve to have four cusps of nearly equal size. The accessory cusp was situated between the right and left coronary cusps. By pulsed Doppler echocardiography, holodiastolic turbulent flow signals were observed in the left ventricle, and the aortic flow pattern showed holodiastolic reverse flow, indicating severe aortic regurgitation. These findings were confirmed by aortography and by surgery. The coronary arteries and pulmonary valve were normal. We attempted a classification of the anatomical variations of the previously reported 34 cases of isolated quadricuspid aortic valves, including our own. They were classified as one smaller (67%), four equal (18%), three smaller (6%), four unequal (6%) and two smaller (3%) types. Twenty of the 34 patients had aortic regurgitation. Bacterial endocarditis and congestive heart failure were the main causes of death.

Aortic Valve↗
PubMed1986

[Analysis of mitral inflow velocity pattern in relation to left ventricular end-diastolic pressure].

The relationship between mitral inflow velocity patterns and left ventricular end-diastolic pressure (LVEDP) was evaluated using pulsed Doppler echocardiography in 34 cases of heart disease, without significant valvular regurgitation. Flow patterns in 19 of the 34 cases were also examined before and after the elevation of LVEDP by methoxamine infusion, 0.01 mg/kg/min. The ratio of the peak velocities in the atrial contraction phase to that in the rapid filling phase (A/R) and the ratio of mean acceleration rates to peak velocities in the rapid filling phase (ACR/R) were determined from the mitral flow patterns obtained by the apical approach. 1. ACR/R correlated significantly with LVEDP (r = 0.49), but A/R did not. LVEDP in six cases with normal A/R (0.5 to 1.0) was 8.3 +/- 2.9 mmHg (mean +/- SD). Among 19 cases with A/R of 1.0 or more and ACR/R less than 13 sec-1, LVEDP showed 10.2 +/- 3.8 mmHg. In eight cases with A/R of 1.0 or more and ACR/R of 13 sec-1 or more, LVEDP was 17.9 +/- 6.2 mmHg. The average value of LVEDP in two cases with A/R less than 0.5 was 18.5 mmHg. 2. When the LVEDP was elevated after methoxamine infusion, A/R within normal range increased in five of six cases and decreased in the remaining case. A/R more than 1.0 decreased in 10 of 11 cases and ACR/R tended to increase with increasing LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Clinical study on beclomethasone dipropionate powder preparation (TL-102) in perennial nasal allergy.

The efficacy, safety and optimal dose of TL-102, a powder mixture of beclomethasone dipropionate (BDP) and hydroxypropylcellulose (HCP) were studied in 250 patients with perennial nasal allergy in an intergroup comparative double-blind manner. Four different capsules containing respectively 30 micrograms of HCP and 1.5 micrograms, 12.5 micrograms, 25 micrograms and 50 micrograms of BDP, were prepared and the drug was applied intranasally evenly between both nostrils at a dose of 2 cap./day b.i.d. for one week. The degrees of overall improvement, usefulness, improvement of nasal symptoms (sneezing, nasal discharge, nasal blockage) and improvement of rhinoscopical findings (mucosal swelling and nasal secretion) were found to be dose-dependent. Antigen provocation reaction and nasal eosinophil count were both inhibited as compared with the TL 1.5 g group. The incidence of side effects was 4.5%, but all side effects observed were mild. Using TL-102 resulted in a therapeutic effect comparable to the conventional BDP preparations using a dose 1/4th of the normal dose of these BDP preparations. The incidence of side effects was 1/3th in comparison with conventional BDP. It was suitable to administer BDP 50 micrograms capsule containing 30 mg of HCP twice a day.

Administration, Intranasal↗
PubMed1986

[Pharmacokinetics of 1-phthalidyl-5-fluorouracil (PH-FU)].

The blood level of PH-FU following oral administration to rabbits and tumor-bearing mice was considerably lower than that of Tegafur, HCFU or 5'DFUR, and decreased more rapidly. The t1/2 beta was 0.48 h (rabbits) and 1.74-1.91 h (mice). The blood level of 5-FU derived from PH-FU was higher at an earlier time after administration than that derived from other 5-FU derivatives, but it disappeared more rapidly. The tissue level of PH-FU in S-180-and Lewis lung carcinoma-bearing mice was detected at a low level in various tissues of mice, except for a higher level in the digestive tract and a lower level in the brain and muscle. The tissue level of 5-FU in both types of mice was high in the digestive tract and kidney. The 5-FU level in the 2 kinds of tumor tissues was relatively high and persisted for several hours. After incubating PH-FU and tissue homogenates from humans and mice at 37 degrees C for 2 h, PH-FU was converted to 5-FU very strongly in the liver and kidney, and considerably strongly in the muscle, heart, tongue and testis. In conclusion, PH-FU seems to be characterized by a low blood and tissue level of unchanged drug, a high production of 5-FU and a short duration of the level.

Administration, Oral↗
PubMed1986

Effect of dosing frequency on the development of physical dependence and tolerance to pentobarbital.

Many studies have suggested the importance of the rate of drug elimination in the development of pharmacodynamic tolerance and physical dependence to sedative-hypnotic drugs. Our previous study demonstrated that the role of individual variation in elimination kinetics played an important part in producing pharmacodynamic tolerance and physical dependence when the drug was given at a fixed dose-frequency schedule. The present study investigated the effect of various dose-frequency schedules on the production of tolerance and physical dependence. Controlling the frequency of administration was thought to be the most rational clinical approach in avoiding the production of tolerance and physical dependence with repeated sedative-hypnotic medication. Groups of animals were treated with Na pentobarbital according to the "maximally tolerable" dosing schedule described previously, except that with different dose-frequency schedules, i.e., twice a day, once every day, once every 1.5 days and once every other day for 70 consecutive doses and then withdrawn abruptly. The relationship between the number of Na pentobarbital doses under each dose-frequency schedule and the pharmacokinetic and pharmacodynamic tolerance production, plus the intensity of withdrawal, were studied. The withdrawal intensity was further correlated to the time lag between each drug administration by estimating the maximal time allowed between doses that does not produce any spontaneous withdrawal convulsions and overt withdrawal signs. It was concluded that the time required for repeated Na pentobarbital administration that does not produce withdrawal convulsion and overt withdrawal signs was 4.9 and 5.7 times the average pentobarbital half-life, respectively.

Animals↗
PubMed1986

[Dose, administration time and route and hepatic function-dependent metabolism of 5-FU in mice].

Pharmacokinetic studies of 5-FU in normal and Sarcoma 180-bearing mice were performed, and the following results obtained: When the administered dose of 5-FU was increased, it was found that there was an increase in the half-life and AUC (area under the concentration curve) and a lower rate of plasma clearance. When the drug was administered at equal doses of 40 mg/kg, the rate of clearance was high in the order of p.o. greater than continuous infusion greater than i.v. bolus. When Sarcoma 180-bearing mice were injected with CCl4 to induce liver dysfunction and subsequently administered 5-FU, the AUCs of 5-FU in the plasma and tumor tissue were increased by 2 and 1.3 times, respectively, as compared with non-treated mice. The Vmax (nmol/mg protein/min) of DHU (dihydrouracil dehydrogenase) in the liver homogenate from normal mice was 1.18 and found to be 0.70 in CCl4-treated mice. In conclusion, the pharmacokinetics of 5-FU were found to be dependent on the dose, infusion time, administration route and liver function, which seem to be correlated with the capacity of the catabolic enzyme, DHU.

Administration, Oral↗