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Biomedical subjects

M Iwaki

Publications and source records attributed to M Iwaki.

At least 163 records · Page 9Linked to original sources
PubMed1989

Dogs hypersensitive to house dust mite.

Active intradermal skin reaction, respiratory resistance and respiratory patterns were examined in five dogs after intradermal injection or inhalation of house dust mite (Dermatophagoides farinae) extract and the results obtained were as follows: 1. Three out of the five dogs exhibited positive skin reactions against house dust mite extract solution at concentrations of 0.1 micrograms/ml to 10 micrograms/ml. 2. Inhalation of mite extract at a concentration of 1 mg/ml by the dogs that had positive skin reactions produced a marked increase in respiratory resistance and changes in spirogram. These results suggest that the dogs that exhibited positive skin reactions were spontaneously sensitized to D. farinae.

Animals↗
PubMed1988

In vitro kinetic studies of the reaction of hydralazine and its acetone hydrazone with pyruvic acid.

To understand the reaction between hydralazine (HP) or its acetone hydrazone (HAH), a metabolite of HP and pyruvic acid, a new selective HPLC method for simultaneous determination of HP, HAH, and hydralazine pyruvic acid hydrazone (HPH) was developed. In vitro degradation of HAH and formation of HP and HPH were investigated at pH 7.4 and 37 degrees C in the presence or absence of pyruvic acid. Hydralazine degraded slowly according to an apparent first-order rate (7.46 x 10(-2)h-1). The degenerative reaction of HAH, accompanied by simultaneous hydrolysis to the parent drug HP, was also subject to apparent first-order loss (3.00 x 10(-1)h-1). In addition, HAH was partly converted to HP and HPH in the presence of pyruvic acid. For the formation pathway of HPH, a model that included the direct reaction of HAH with pyruvic acid and the secondary formation mediated by back-conversion to HP gave a better fit to the experimental data than the model consisting of the latter reaction only. About 10% of the HPH formed was generated by the direct reaction of HAH with pyruvic acid, based on the rate constants estimated. These results suggest that the formation of HPH is not all accomplished through back-conversion to HP.

Chemical Phenomena↗
PubMed1988

Tetraethylammonium-induced contraction of rabbit coronary artery.

The vasoactive effect of tetraethylammonium (TEA), a well-known K channel blocker, was tested on helical strips excised from the large epicardial coronary arteries of rabbit hearts. TEA (10 mM) induced transient tetanic contraction of greater amplitude as a result of summation of twitch responses. Occasionally, spontaneous periodic contractions occurred during prolonged exposure to 10 mM TEA. This TEA-induced contraction was abolished in Ca-free solution and suppressed by Ca-entry blockers: nitroglycerin, nicorandil, and isoproterenol, but not by phentolamine or atropine. In strips in which TEA did not induce remarkable contraction, subsequent addition of a subthreshold concentration of ergonovine, serotonin, acetylcholine, ouabain, K-rich solution, or alkalinization of the solution provoked remarkable contraction. These results are consistent with previous reports that TEA induced tetanic contraction as a result of summation of twitch responses due to spontaneous discharge of Ca-spikes in some arterial and tracheal smooth muscle. The results also support the idea that TEA-induced contraction of the rabbit coronary artery is mediated by the same mechanism, i.e., spontaneous Ca-spike discharge.

Animals↗
PubMed1988

A simple purification method for a glucosyltransferase complex from Streptococcus mutans OMZ 176 with a high yield.

1. Glucosyltransferase was purified from Streptococcus mutans OMZ 176 by ammonium sulfate fractionation and gel filtration. 2. The overall purification was about 15,000-fold with a yield of 53%. 3. The purified enzyme appeared to be a multienzyme complex consisting of three different components with molecular weights of 158,000, 153,000 and 149,000, respectively.

Ammonium Sulfate↗
PubMed1988

The percutaneous absorption of propranolol and prediction of the plasma concentration.

In order to avoid first-pass metabolism and to maintain therapeutically effective concentration of propranolol (PL) for a prolonged time, ointments of PL were prepared and the percutaneous (p.c.) absorption was investigated in rabbits. To describe the plasma PL concentration profile during repeated p.c. administrations, a simple pharmacokinetic model, including a first-order absorption process, was applied. The p.c. absorption of PL from both macrogol (400:4000, 30:40, g/g) and Carbopol 934 ointments was significantly increased by adding Azone (AZ). Effective plasma levels were sustained for about 10-20 h, but the absorption of PL from the macrogol ointment was relatively slow. The bioavailability of PL in the 5% PL Carbopol ointment with AZ was 13%. The plasma level of PL after application of Carbopol ointment was enhanced as PL was increased in the ointment, 3 to 5%. The repeated p.c. absorption studies were carried out by applying the 5% PL ointment daily for 3 d. The use of the pharmacokinetic model was justified by good agreement with the observed data after repeated applications of the ointment. Thus, the plasma PL concentration profile during repeated p.c. administrations can be predicted using the model.

Administration, Cutaneous↗
PubMed1988

A pharmacokinetic model for percutaneous absorption of valproic acid and prediction of drug disposition.

To predict the plasma concentrations after percutaneous application of valproic acid (VPA), we presented a new pharmacokinetic model which includes simultaneous two absorption processes through the skin. The simulation contains four first-order rate constants for the following: a) absorption via the lipid and water routes in skin and b) uptake from the skin into systemic circulation and subsequent elimination. The fitness of the model presented for experimental data was compared with simple one-compartment models. As a result, the new model was successfully able to describe the time course of the plasma VPA concentrations following percutaneous application of the ointments. VPA was found to be rapidly absorbed across the water routes (ka1 = 2.60 h-1), which accounted for about 70% of the total, followed by a lasting absorption via the lipid routes (ka2 = 0.108 h-1). The pharmacokinetic model with parallel lipid and aqueous pore skin transport pathways in skin was more adequate for the interpretation of p.c. absorption data of VPA than the models with an absorption process.

Administration, Cutaneous↗
PubMed1988

Thermodynamic study on enhancement of percutaneous penetration of drugs by Azone.

The mechanism whereby Azone (AZ, 1-dodecylazacycloheptan-2-one) enhances drug penetration through the hairless rat abdominal skin was investigated thermodynamically. Three kinds of drugs, indomethacin, ibuprofen and sulfanilamide which have similar solubilities in a mixed organic solvent (ethanol-diethylcarbitol, 40:60 v/v), were selected to evaluate the drug penetration with or without 5% AZ. Transdermal delivery rates were determined at 27 and 37 degrees C by using an in vitro diffusion cell procedure and the abdominal full-thickness skin of hairless rat. The solubility of each of the three drugs in the solvent with AZ was similar to that without AZ. Ethanol in the vehicle penetrated through the skin prior to the drugs. Activation energies for the skin penetration of the three drugs in the presence of AZ were decreased compared to those in its absence. For all drugs the partition coefficients between the skin and vehicle with AZ were 2-80 times higher than those without it. The activity coefficients of drugs in the presence of AZ in the skin were 2-90 times lower than those without the enhancer. These results suggested that the enhancing effect of AZ was not due to changing the solubility of the drugs in solvents but to increasing the thermodynamic activities and the affinities of the drugs to skin.

Administration, Cutaneous↗
PubMed1987

Inhibitory effects of FUT-175, a new synthetic protease inhibitor, on intravascular hemolysis by human serum in mice.

Effects of FUT-175, a new protease inhibitor, on intravascular hemolysis of mouse erythrocytes caused by intravenous injection of human serum was studied in mice. In in vitro experiments, unsensitized erythrocytes obtained from various species of animals were lysed with sera in EGTA-GVB-Mg++. After heat inactivation of sera at 50 degrees C for 30 min, hemolysis in EGTA-GVB-Mg++ was abolished, indicating loss of activity of the alternative complement pathway. FUT-175 inhibited the alternative complement pathway-mediated hemolysis with IC50 values of 1.3 X 10(-7) to 4.0 X 10(-7) M. Intravenous injection of human serum caused intravascular hemolysis of mouse erythrocytes in mice. No remarkable change was observed in the mice that were injected with heat-inactivated (56 degrees C, 30 min) human serum. Intravenous administration of FUT-175 at a dose of 3 or 10 mg/kg inhibited intravascular hemolysis of mouse erythrocytes regardless of whether it was administered before or after injection of human serum. These results indicated that FUT-175 prevents intravascular hemolysis of mouse erythrocytes through the inhibitory effect of both alternative and classical complement pathway.

Animals↗
PubMed1987

Effects of FUT-175, a novel synthetic protease inhibitor, on the development of adjuvant arthritis in rats and some biological reactions dependent on complement activation.

1. The effects of FUT-175 on the development of adjuvant arthritis in rats were studied and compared with those of indomethacin. FUT-175 inhibited both primary and secondary paw lesions in the adjuvant arthritic rats when it was administered orally on a daily basis from the day before through 18th day after adjuvant injection. 2. In addition, FUT-175 inhibited the increase in hemolytic complement in adjuvant arthritic rats in a dose-dependent manner. 3. Indomethacin also showed an inhibitory effect on the development of arthritic lesion, but had no effect on the increase in hemolytic complement in the adjuvant arthritis in rats. 4. Furthermore, FUT-175 inhibited the activities of various proteases in vitro, and then strongly inhibited complement-mediated hemolysis via the classical and alternative pathways, while indomethacin had no effect on them. 5. These results suggest that the anti-inflammatory activity of FUT-175 may differ from indomethacin in the mechanisms of action and, at least in part, due to the anti-complement activity.

Animals↗
PubMed1987

Tetraethylammonium induced coronary spasm in isolated perfused rabbit heart: a hypothesis for the mechanism of coronary spasm.

The vasoactive effect of tetraethylammonium, which is known to reduce potassium conductance of the membrane of arterial smooth muscle cells, was tested on large epicardial coronary arteries in isolated perfused rabbit hearts. These hearts were perfused selectively through the right and left coronary arteries. Left coronary angiography was performed using Krebs-Henseleit solution containing phenolsulfonphthalein under constant pressure, and the epicardial electrogram was recorded. In 59 of 114 hearts 30 mmol.litre-1 tetraethylammonium induced severe constriction of the left epicardial coronary artery, which was associated with electrocardiographic ST segment elevation in some cases. The induced spasm was prevented by diltiazem (200 nmol.litre-1), glyceryl trinitrate (2 mumol.litre-1), or nicorandil (10 mumol.litre-1), but not by phentolamine (1 mumol.litre-1) or atropine (1 mumol.litre-1). In hearts in which tetraethylammonium did not induce spasm, subsequent addition of ergonovine (100 nmol.litre-1) or alkalinisation of the perfusate (pH 7.65-7.70) provoked spasm. The tetraethylammonium induced spasm resembled the coronary spasm seen in patients with variant angina and was a reproducible in vitro model of coronary spasm. These observations support the hypothesis that the primary defect in patients with coronary spasm is decreased potassium permeability of the membrane of coronary arterial smooth muscle cells.

Animals↗
PubMed1987

Measurement of human urokinase activity in plasma by using mono-specific antibody-conjugated paper disk.

Human urokinase (HUK) was purified from commercial product by high performance liquid chromatography on TSK GEL-G3000SW and affinity chromatography on benzamidine-Sepharose 4B. The purified enzyme was of a high molecular weight form (molecular weight of 53,000). This preparation was utilized as an antigen to immunize rabbits; the obtained antibody showed a high specificity against HUK. The antibody was conjugated to CNBr-activated paper disks. The antibody-conjugated paper disk and a fluorogenic peptide substrate, glutaryl-Gly-Arg-4-methyl-coumarine-7-amide, were used to measure urokinase (UK) activity in plasma. The calibration curve obtained by the proposed method passed through the origin and was linear in the range of 0-0.16 IU of HUK. The incubation of HUK with an excess amount of alpha 2-macroglobulin at 37 degrees C for 3 h gave only about a 30% decrease of the activity assayed by the proposed method. After incubations of HUK with alpha 1-antitrypsin and antithrombin III, the activity was completely inhibited. The incubation of HUK with plasma at 37 degrees C decreased the activity as a function of time. However, when the antibody-conjugated paper disk was used for the immunoreaction to HUK in plasma at 4 degrees C, no decrease of UK activity was observed. The plasma decay curve of UK activity after a single intravenous (i.v.) injection of HUK into a rabbit (12,000 IU/kg) indicated bi-exponential kinetics by using this assay method. The rate constants of the alpha and beta phases were 0.120 +/- 0.020 and 0.021 +/- 0.002 min-1, respectively. These result suggest that the proposed method is useful for measuring UK activity in plasma of patients with intravascular coagulation after i.v. administration of UK.

Animals↗
PubMed1987

Prediction of plasma concentration profile during single and repeated skin applications of indomethacin and its calcium salt ointments.

To determine the plasma concentrations and to clarify pharmacokinetic behavior from a pharmaceutical application viewpoint, indomethacin (IND) and its calcium salt (IND-Ca) in the form of gel ointments were applied singly and repeatedly to rat abdominal skin under occlusions. In order to describe the plasma IND concentration profile during repeated percutaneous administration, a highly simple pharmacokinetic model including a first-order absorption process with a lag time was applied. IND and IND-Ca were readily absorbed with a short lag time from IND-Ca ointment (1% as IND, 0.14 g/cm2, 3.0 x 1.2 cm area) containing Azone. Even when the applied dose of IND-Ca ointment was decreased to one-fourth (1.0 x 1.0 cm area), the plasma IND concentrations were maintained above the effective levels for 24h. The use of the pharmacokinetic model was justified by good agreement with observed data obtained after repeated percutaneous application of ointments. Thus, the plasma IND concentration-time courses during repeated percutaneous administration can be predicted by using the model.

Administration, Topical↗
PubMed1987

Percutaneous absorption of valproic acid and its plasma concentration after application of ointment.

In order to develop a percutaneous (p.c.) dosage form of valproic acid (VPA), ointments containing VPA and both VPA and its calcium salt (VPA-Ca) were prepared. The p.c. absorption was studied by determining the plasma concentrations of VPA in rabbits following application of either ointment. In addition, the in vitro penetration study with excised full-thickness rabbit skin was done to evaluate the pharmaceutical availability. VPA was readily and rapidly absorbed through the skin from the gel ointment. The plasma concentrations of VPA higher than 30 micrograms/ml were maintained for 6 h after application of 5% VPA.5% VPA-Ca gel ointment, and for 4 h after application of 5% VPA ointment. The bioavailability of VPA following dosing of both ointment was above 97%. The in vitro penetration rate through the skin and skin/solvent partition coefficient were significantly lower with 5% VPA.5% VPA-Ca solution than with 5% VPA, suggesting the slower penetration of VPA from the 5% VPA.5% VPA-Ca. A small difference was observed in the release rate of drugs from these ointments. The present results demonstrated the pharmaceutical effectiveness of the VPA.VPA-Ca ointment for seizure disorders.

Animals↗
PubMed1987

Encapsulation of human urokinase in rabbit erythrocytes and its disposition in the circulation system in rabbits.

The application and usefulness of resealed erythrocytes as cell carriers of human urokinase (UK) were studied in rabbits. UK purified by affinity chromatography were used to load erythrocytes by a dialysis method. The amount of UK entrapped in the erythrocytes was 2064 +/- 416 IU per ml of packed cells, with efficiency of encapsulation being 20.0 +/- 4.2%. When the UK loaded erythrocytes were incubated in Hank's solution or rabbit plasma for 3 h at 37 degrees C, the UK activities in the resealed cells declined similarly to first-order kinetics. The UK activities released into Hank's solution increased cumulatively during the incubation but those in plasma decreased after a peak concentration at 15 min. After i.v. administration of free UK, the activity decreased according to a biexponential function, suggesting its uptake in the liver and kidney and the formation of UK-proteinase inhibitor complexes and the in vivo decline of UK in loaded cells also indicated a biexponential kinetics. The AUC ratio of UK after an intravenous injection of the loaded erythrocytes was calculated to be about 8.0%. These results indicated that the UK loaded erythrocytes may be useful as a dosage form for treatment of patients with thrombosis.

Animals↗