Search PubMed⌕ Search

Biomedical subjects

Y Sawada

Publications and source records attributed to Y Sawada.

At least 325 records · Page 18Linked to original sources

Reproducible increases in blood pressure during intermittent noise exposure: underlying haemodynamic mechanisms specific to passive coping.

The purpose of the present study was to investigate the reproducibility of the increases in blood pressure found in our recent study on exposure to intermittent noise, to confirm the haemodynamic mechanism raising blood pressure (via an increase in peripheral vascular resistance expected to be specific to passive coping), and to assess baroreceptor cardiac reflex sensitivity in connection with the blood pressure elevation. A group of 16 young normotensive men participated in the experiment and underwent a 10-min intermittent exposure to pink noise at 100 dB (sound pressure level). The subjects also underwent three other stresses: a 1-min cold pressor test, a 3-min isometric handgrip and 3-min of mental arithmetic. The results indicated that blood pressure was elevated reproducibly for most of the noise exposure periods and that peripheral vascular resistance increased simultaneously, as expected. Baroreflex sensitivity was not suppressed. The results, as a whole, were in agreement with our recent findings for exposure to a similar type of noise and thus the reproducibility was corroborated. The mechanism raising blood pressure was similar in the cold pressor test. Conversely, during the isometric handgrip and mental arithmetic, blood pressure elevations were attributable mainly to increases in cardiac output. The implications of the opposing haemodynamic mechanisms raising blood pressure among the four stressful tasks have been discussed in relation to active versus passive coping required for each task. Differences in the magnitude of suppression observed in baroreflex sensitivity among the tasks have also been discussed in the context of defence reactions.

Acoustic Stimulation↗

Prediction of the therapeutic dose for beta-stimulants based on preclinical data: application of oral dosage forms and aerosols to asthmatic patients.

The therapeutic doses of beta-stimulants in the treatment of bronchial asthma show wide variation among the drugs. In the present study, we tried to construct a system for prediction of the optimum clinical dose of beta-stimulants as oral dosage forms and aerosols using the data from preclinical pharmacological studies and pharmacokinetic data in humans. Values of EC50 (drug concentration that gives the half-maximum bronchodilator effect) in the in vitro studies based on isolated trachea of guinea pigs were collected from the literature. The ratios of the EC50 value of each drug to that of isoproterenol were used as the indicator of in vitro pharmacological activity. There were significant correlations between the EC50 ratios and the oral dose or the maximum plasma concentration after single oral administration, but the correlation coefficients were relatively small (r < .9). On the other hand, a linear log-log relationship was observed between the EC50 ratio and the maximum plasma unbound concentration (Cu(max)) (slope = 0.907, r = .955, p < 0.001). In the case of aerosols, a good correlation was observed between the EC50 ratio and the dose (slope = 0.770, r = .900, p < 0.01). The predicted concentration of beta-stimulants in the lung after aerosol administration tended to be higher than the Cu(max) after oral administration, suggesting the contribution of nonspecific binding in the lung tissue. These findings indicate the possibility of predicting the appropriate dose of beta-stimulants based on the preclinical pharmacological data and the pharmacokinetic data in humans.

Administration, Oral↗

Classification of benzodiazepine hypnotics in humans based on receptor occupancy theory.

Benzodiazepine (BZP) hypnotics are now classified into four groups according to their plasma elimination rates: ultrashort-, short-, intermediate-, and long-acting drugs. Since the specific binding affinities for the BZP receptor vary widely among the BZPs and their active metabolites, it may be more reasonable to correlate their pharmacological activities with the BZP receptor occupancy rather than with their plasma concentrations. The time courses of total plasma concentrations of BZPs and their active metabolites after a single oral administration were obtained from the literature, and their unbound concentrations (Cu) were calculated from the reported values of their plasma unbound fractions. The data of the receptor binding affinities of the BZPs, reported as dissociation constants (Kd) determined by in vitro binding experiments, were also obtained from the literature. Using these values, the time courses of receptor occupancies [Cu/(Kd + Cu) x 100%] were calculated for the various BZPs. A mutual competitive inhibition was considered in the case of the drugs that had active metabolites. Although plasma total and unbound concentration time profiles of the BZPs showed a wide variation, similar patterns were obtained for the time courses of the receptor occupancy among the BZPs in each group, indicating that the BZP hypnotics can be classified more conveniently based on receptor occupancy theory.

Animals↗

Release of Ofloxacin from silicone gel sheet.

From a drug delivery system using silicone gel, the amount of Ofloxacin (OFLX) released or transferred to a wound and blood was measured over 2 weeks. From three types of silicone gel containing 2, 0.2 and 0.02% OFLX respectively, levels from that with 2% OFLX were highest, approximately two to five times higher than that with 0.02% OFLX. Statistically significant differences were found between the three types (P < 0.01, Student's t-test). When used in partial thickness skin wounds on rats, only an extremely small amount of OFLX was detected in the serum, being higher under gel containing 2% OFLX. In a clinical study, however, no drug was detected either in the blood or the wound after 1 week.

Adolescent↗

The relationship between time of application of prostaglandin E1 and improved flap survival.

Using 60 Hirosaki hairless rats, the relationship between the time of starting topical administration of Prostaglandin E1 using silicone gel and flap survival rate is described. Compared to control groups, beginning the administration of PGE1 at 0 (P < 0.01) and 3 h (P < 0.05) after flap elevation resulted in an increased flap survival area (Student's t-test). However, in groups in which PGE1 administration was begun at 6, 9 and 12 h after flap elevation, no statistically significant differences could be detected.

Administration, Topical↗

A study of topical and systemic prostaglandin E1 and survival of experimental skin flaps.

A study has been undertaken to investigate Prostaglandin E1 administration procedure for improving flap survival. Whether the drug was administered continuously or transcutaneously using a silicone gel drug delivery system; or was topically injected into the critical zone of the flap; or was intraperitoneally administered intermittently over an hour after surgery a statistically significant improvement of flap survival occurred (P < 0.01, Student's t-test). However, no improvement of flap survival was seen when the drug was administered only once intraperitoneally immediately after flap elevation, although administered doses of the drug in those rats was equal to the doses in the rats which received intermittent administration of the drug intraperitoneally over an hour after surgery.

Administration, Cutaneous↗

Pressure developed under pressure garment.

To study how much pressure develops under a pressure garment, and how to obtain adequate effective pressure for scar treatment, we have used garments in combination with sponge and plastic plates in human volunteers. The pressures increased significantly when a sponge or sponge and plastic plate were used beneath the garment compared to pressures using a garment alone. In evaluations in patients with scar tissue on the limb, similar findings resulted.

Adolescent↗

Concentration of orally administered antimicrobial agent in burn scar tissue, granulation tissue, normal skin and serum.

Tissue and serum concentrations of orally administered ofloxacin were measured using high performance liquid chromatography. From 56 patients who received 200 mg of ofloxacin prior to surgery, 103 specimens including 48 of serum, 32 of scar tissue, 18 of normal skin and five of granulation tissue were harvested between 2 and 3 h after administration. The ofloxacin values were 1798.6 +/- 1125.5 ng/g in the granulation tissue followed by 1525.5 +/- 1002.7 ng/ml in the serum, 1450.0 +/- 1011.3 ng/g in the scar tissue and 1092.8 +/- 593.3 ng/g in normal skin. There was no statistically significant difference between the ofloxacin concentrations in those four specimens by ANOVA test.

Administration, Oral↗

Expanding oral plastic splint for burn patients.

An expanding oral plastic splint for preventing microstomia from deep facial burns is described. This splint adjusts to suit the affected oral angles without the need for taking any impression before fabrication. It is especially suitable for severely injured patients starting from the early period shortly after injury, even if the patient has been intubated. Furthermore the expansion forces can be controlled easily according to the degree of contracture.

Adult↗

Effect of trapidil on serum lipid and apolipoprotein levels in patients with ischemic heart disease.

1. Serum total cholesterol (TCH), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein (LDL-C), atherosclerotic index (AI) and apolipoprotein (apo A-I, A-II, B, C-II, C-III and E) levels were investigated in patients with ischemic heart disease before and after medication of trapidil. 2. Twenty-one patients were orally given 100 mg of trapidil, three times daily (300 mg/day). After 8 weeks' administration, serum HDL-C level increased (P < 0.01) and AI decreased (P < 0.02) significantly, whereas TCH, TG and LDL-C levels tended to decrease but not significantly. 3. Among the parameters of apolipoproteins, apo A-I, a main protein of HDL-C, was significantly increased (P < 0.05) by trapidil. 4. These results indicate that trapidil has a beneficial effect on the coronary risk profile as reflected by lipid measurements.

Aged↗

Comparison of the hepatic uptake clearances of fifteen drugs with a wide range of membrane permeabilities in isolated rat hepatocytes and perfused rat livers.

The hepatic uptake clearances of 15 ligands with a wide range of permeabilities were determined in rats using two techniques: centrifugal filtration with isolated hepatocytes and the multiple indicator dilution (MID) method with isolated perfused livers. Some of the uptake clearance values were taken from the literature. Uptake clearance values obtained from isolated hepatocytes were extrapolated to that per gram liver (PSinf.cell), assuming that 1 g of liver has 1.3 x 10(8) cells. The values of PSinf.cell varied from approximately 0.1 to 72 (mL/min/g liver). The values of PSinf.cell were similar to those (PSinf.MID) determined by the MID method for ligands with uptake clearances below approximately 1 mL/min/g liver. However, for the ligands with larger uptake clearances, the PSinf.MID values were lower than the PSinf.cell values and appeared to reach an upper limit (approx. 15-20 mL/min/g liver). The PSinf.cell values of 1-propranolol, tetraphenylphosphonium (TPP+), and diazepam were 72, 43, and 22 mL/min/g liver, respectively, whereas their uptake clearances (PSinf.MID) determined by the MID method were 4 to 10 times lower. One of the possible mechanisms for this discrepancy is that an unstirred water layer, which may exist in Disse's space in isolated perfused livers (and probably under in vivo condition), limits the hepatic uptake rate of ligands with extremely high membrane permeabilities.

Animals↗

Case report: a case of multiple coronary artery to left ventricular communications.

A 39-year-old man with anginal pain had multiple coronary artery to left ventricular communications. His electrocardiogram showed evidence of left ventricular hypertrophy, and an echocardiogram revealed a dilated left ventricle. A coronary angiogram revealed multiple coronary artery to left ventricular fistulae involving three major coronary arteries with no evidence of atherosclerotic lesions. Only 17 cases of such fistulous communications involving three major coronary arteries have been reported in the literature. It is suggested that the fistulous communications to the left ventricle was a cause of his angina pectoris, probably because of the coronary steal phenomenon.

Adult↗

Alterations in pressure under elastic bandages: experimental and clinical evaluation.

Clinical and experimental studies of pressure under elastic bandages are performed in order to assess their effectiveness in compressing wounds to prevent edema in burn wounds. In experimental studies, pressure decreased slowly over a day when applied with a tension of 250 grams to a limb model without a pad. However, pressure decreased a little more rapidly when applied using a pad, especially when the pad became wet. In clinical studies among patients, the pressure under the elastic bandage decreased more rapidly over time than it did in the experimental studies. From those findings, although harmful side effects such as circulatory disturbances will not occur when an elastic bandage is applied on the limb with a tension of 250 grams, it is very difficult to maintain the initial level of pressure correctly and control the pressure for even the duration of a single day clinically.

Adolescent↗

Dose-dependent hepatic handling of l-propranolol determined by multiple indicator dilution method: influence of tissue binding of l-propranolol on its hepatic elimination.

Concentration-dependency in the hepatic elimination of l-propranolol (l-PR) was investigated over a wide range of concentrations from 60 to 2200 microM in an isolated rat liver perfusion system. Under the steady-state condition produced by unlabeled l-PR at various concentrations, 3H-l-PR and 14C-inulin were bolusly injected into the portal vein, and the outflow was collected at 0.5 s intervals over 30 s. Up to 300 microM, the instantaneous hepatic availability of l-PR was approximately 4%, while it abruptly increased when the perfusate concentration exceeded 300 microM. To determine which process (influx or efflux or sequestration process) caused the nonlinearity, we calculated the rate constants k1 (influx), k2 (efflux), and k3 (sequestration) based on the "distributed" model. With increasing l-PR concentration in the perfusate, k2 increased approximately two times, whereas k3 decreased to approximately one-half. In contrast, k1 was independent of the perfusate concentration. The concentration-dependency of k2 was explained by saturation of l-PR tissue binding, since the tissue unbound fraction of l-PR obtained with liver homogenates and isolated hepatocytes increased approximately two times. The efflux and sequestration clearances were then normalized by the unbound fractions in the liver. The efflux clearance for unbound l-PR was constant irrespective of the perfusate concentration, whereas the sequestration clearance for unbound l-PR (CL(int) showed Michaelis-Menten type saturation (Km = 28 microM, Vmax = 2.8 mumol/min/g liver, alpha (nonspecific) = 2- ml/min/g liver).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prediction of therapeutic doses of beta-adrenergic receptor blocking agents based on quantitative structure-pharmacokinetic/pharmacodynamic relationship.

The usual therapeutic doses for the treatment of both angina pectoris and cardiac arrhythmia vary widely among beta-blocking agents, with a maximum of about a 200-fold difference, despite subjects' same clinical improvement at the varying doses. In order to clarify the mechanism of this difference, we analyzed retrospectively the cardiac pharmacological activities of beta-blocking agents based on the receptor occupancy theory by using both their unbound concentrations in plasma at steady state (Cssf), as well as dissociation constants (KB and KI, which were determined by in vitro binding experiments and by in vitro pharmacological experiments, respectively) for a beta 1 receptor. A significant log-linear relationship between Cssf and the KB values was obtained with a slope of regression line of 0.91 (r = 0.83, p < 0.01). On the other hand, the correlation coefficient of the relationship between Cssf and the KI values was low, with a slope of about 0.5 (r = 0.80, p < 0.01). The beta 1 receptor occupancies calculated from KB values at the steady state condition after the oral administration of usual doses were almost constant (80.5 +/- 16.8%), regardless of the wide variation of usual doses of the drugs. This result indicated that the receptor occupancy may be an appropriate indicator for the pharmacological activity of the drug. Furthermore, there were significant relationships between the primary pharmacokinetic parameters: Cb/Cf, CLtot/F, and Vdssf, and the octanol/water partition coefficient (PC), with correlation coefficients of 0.80, 0.50 and 0.85, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Sensitive determination of ambenonium in plasma using inhibitory activity to acetylcholinesterase.

A sensitive analytical method for the determination of ambenonium, a selective acetylcholinesterase inhibitor, in plasma was developed. The procedure involves ultrafiltration to remove endogenous plasma cholinesterase, followed by colorimetric measurement of the inhibitory activity to acetylcholinesterase by the thiocholine method. Coefficient of variation of within-day triplicate analysis is less than 20% at the concentration of 5 nM. Detection limit of this method is 1 nM, which is twice lower than the most sensitive HPLC method reported previously. This assay procedure is applied to the pharmacokinetic study of ambenonium after intravenous administration of low dose (10-20 nmol/kg) to rat. This new method is rapid and simple and makes it possible to determine the ambenonium concentration in plasma with good accuracy.

Acetylcholinesterase↗

Inhibition of GABAA receptor-mediated current responses by enoxacin (new quinolone) and felbinac (non-steroidal anti-inflammatory drug) in Xenopus oocytes injected with mouse-brain messenger RNA.

The convulsant interaction between enoxacin (ENX), a new quinolone antibacterial agent (NQ), and felbinac (FLB), a non-steroidal anti-inflammatory drug (NSAID), in vivo was reproduced as the change of GABA-induced current response in Xenopus oocytes injected with mouse brain mRNA. GABA (10 microM) response was inhibited by ENX in a dose-dependent manner, and IC50 of ENX was 96 microM. Moreover, the inhibitory effect of ENX was 80-fold potentiated in the presence of 10 microM FLB. The GABAA-antagonistic interaction between these two drugs in vitro was considered a possible mechanism of convulsant reaction after concomitant administration of NQs and NSAIDs in vivo.

Animals↗

The influence of glucagon on the hepatic transport of taurocholate in isolated perfused rat liver: kinetic analysis by the multiple indicator dilution technique.

Glucagon has been demonstrated to stimulate the uptake of bile acid in isolated rat hepatocytes (Am. J. Physiol., 249, G427 (1985)). In the present study, we determined the influence of glucagon on the hepatic transport of a bile acid, taurocholate (TCA), in isolated rat livers. A single-pass perfusion and a rapid-injection, multiple indicator dilution method were employed. The hepatic availability at steady-state was 0.04. With the presence of glucagon in the perfusate (from 10(-9) to 10(-7) M), the bile flow rate was stimulated by 30%, while hepatic availability was decreased from 0.04 to 0.02 with a stepwise increase in glucagon concentration. Thirty min after the infusion of glucagon (300 nM), [3H]TCA and [14C]inulin were injected in a bolus state into the portal vein, and the outflow was collected at 1.0 s intervals over 30 s. Glucagon decreased the instantaneous hepatic availability by 50% compared to the control level, and was thus compatible with the steady-state experiments. In the control experiment, the influx clearance (PSinf) was 20 times higher than the efflux clearance (PSeff). Glucagon (300 nM) in the perfusate enhanced PSinf by 50% of the control, whereas sequestration clearance (CLseq) and the biliary excretion rate constant remained unchanged. PSeff was stimulated to 2 times the control, but still remained much smaller than CLseq. Based on the comparison of PSinf, PSeff and CLseq, the rate-determining process of TCA hepatic elimination was the influx process in both the presence and absence of glucagon. Taken together, the enhancement of the influx process was responsible for the decrease in TCA hepatic availability caused by glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗