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Biomedical subjects

T Suganuma

Publications and source records attributed to T Suganuma.

At least 127 records · Page 7Linked to original sources
PubMed1983

Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit. I. Single dose study.

The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n = 6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p less than 0.05) effect on plasma theophylline clearance (0.051 +/- 0.006 vs 0.035 +/- 0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p less than 0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference - 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p less than 0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p less than 0.05, r = 0.693, n = 10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drug-metabolizing enzyme.

Administration, Oral↗
PubMed1983

A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta-blockade and steady-state pharmacokinetics.

The relationship between the oral dosage and plasma concentration of the long-acting cardioselective beta-adrenoceptor blocker atenolol and the antihypertensive response to the the degree of beta-adrenoceptor blockade and change in plasma renin activity (PRA) was evaluated in patients with mild-to-moderate essential hypertension in a double-blind, randomized, between-patient, dose-ranging (25, 50 or 100 mg once daily for 4 weeks) study. The optimum, or minimum, daily dose of atenolol to treat patients with mild-to-moderate hypertension was not clearly identified in this study. A between-treatment comparison did not demonstrate that all blood pressure falls were always less in the 25 mg group than in the other two groups. Calculation of beta-error or the power for the negative results between doses suggested that a large sample size is required to draw a conclusion that no dose-antihypertensive relationship of atenolol exists in the treatment of mild-to-moderate hypertension. A relatively flat plasma concentration-antihypertensive response relationship was observed. Steady-state plasma concentrations of atenolol were dose-related and renal drug clearance was well correlated with individual creatinine clearance. beta-adrenoceptor blockade was better correlated with plasma atenolol concentration. Correlations which were less strong were between plasma drug concentration and change in various blood pressures and between blood pressure falls and beta-adrenoceptor blockade. There was no relationship between the fall in blood pressure and change in PRA. Atenolol appeared to suppress PRA in an all-or-none fashion.

Adult↗
PubMed1983

[Human yolk sac tumor of the thymus heterotransplanted into nude mice].

A human yolk sac tumor of the thymus (YSK-1) was transplanted into athymic nude mice. Histological and ultrastructural investigations revealed that the YSK-1 tumor, even after serial transplantation in nude mice, characteristically displayed Schiller-Duval bodies, endodermal sinus structures and ultrastructural profiles, numerous microvilli, desmosome-like cell attachments, annulate lamellar structures, many lipid droplets and interspersed glycogen particles. Serological study by radioimmunoassay demonstrated AFP, CEA, HCG, alpha 1-AT and transferrin in the sera and cyst fluid of the tumor-bearing nude mice. Immunohistochemical investigation using the PAP method showed that the YSK-1 cells produced CEA, HCG, alpha 1-AT, transferrin as well as AFP. The increase in the level of AFP paralleled the increase in tumor size.

Adult↗
PubMed1982

Re-examination of digoxin dosage regimen: comparison of the proposed nomograms or formulae in elderly patients.

1 Comparison of measured trough serum digoxin concentrations (SDC) with those predicted at steady-state by forty sets of previously described pharmacokinetic equations in conjunction with either measured or estimated creatinine clearance (Clcr) was made in an elderly group of patients with varying Clcr (25-89 ml/min) who received maintenance digoxin therapy. 2 Mean values of day-to-day variation (% coefficient of variation) for serum creatine and measured Clcr examined three times within a week in 7 of 40 elderly patients were 6.42 and 8.36% respectively, while this value for SDC was 12.46%. 3 There was a statistically significant correlation (r = 0.72 to 0.79, P less than 0.001, n = 40) between measured Clcr and that estimated from three different methods. Siersbaek-Nielsen's nomogram approach gave the best correlation. 4 The calculated correlation coefficient values between measured and predicted SDC lay within a relatively narrow range but were weak (r = 0.443-0.628). Prediction error analysis, however, allowed us to determine the best set of pharmacokinetic equations for a first approximation to appropriate digoxin maintenance dosage requirements, namely Gault-estimated elimination rate constant, measured Clcr, and Jusko-estimated volume of distribution.

Aged↗
PubMed1981

Comparative histochemical study of alimentary tracts with special reference to the mucous neck cells of the stomach.

Combinations of recently developed paradoxical concanavalin-A staining (PCS) and other routine histochemical procedures have made it possible to classify mucosubstances more precisely. By taking advantage of these sequences, the present study was undertaken both to characterize the mucinous contents of alimentary tracts of several animal species, and to compare the variability of epithelial mucosubstances with special reference to the mucous neck cells of the stomach. The alimentary tracts obtained from 7 species of fish, 5 amphibians, 3 reptiles, 4 birds, and 6 mammals were used. Acidity of epithelial mucosubstances was highly variable even among the corresponding mucous cells. On the contrary, concanavalin-A reactivity seemed to be consistent with each cell and species. The mucous neck cells, which were observed in amphibians, reptiles, and mammals, consistently exhibited a characteristic mucosubstance with stable class-III reactivity by PCS. Inversely, stable class-III reactivity was found only in species possessing mucous neck cells, and was widely distributed in the esophageal glands of the frog, snake, and man; in esophageal mucous cells of the frog and skink; in pyloric glands of amphibia, reptiles, and mammals; and in Brunner's glands of mammals. These mucous cells seem to form an unique group with morphological and histochemical similarities. It is likely that the stable class-III reactivity by PCS is a hallmark of the mucous neck cells and related glands and that, in addition, concanavalin-A reactivity of mucosubstances is evolutionarily more fundamental characteristic.

Amphibians↗
PubMed1981

Ultrastructure and immunohistochemical staining of a transplanted endodermal sinus tumor.

An endodermal sinus (yolk sac) tumor was successfully transplanted into athymic nude mice. Histologic and ultrastructural investigations revealed that the transplanted tumor had a characteristic appearance with numerous Shiller-Duval bodies, endodermal sinus structures and ultrastructural profiles as previously described in human material. The endodermal sinus tumor and normal human yolk sac have been found to synthesize not only alpha-fetoprotein (AFP), but also other serum proteins, namely, albumin, prealbumin, alpha 1-antitrypsin, and transferrin. Serological study by radioimmunoassay demonstrated AFP, carcinoembryonic antigen (CEA) and human chorionic gonadotropin (HCG) in the sera of the tumor-bearing nude mice and in cyst fluid from the transplanted tumor. Immunohistochemical investigation using the unlabeled antibody peroxidase-antiperoxidase method showed using the unlabeled antibody peroxidase-antiperoxidase method showed that the tumor cells produced CEA, alpha 1-antitrypsin, transferrin, HCG as well as AFP. These immunohistochemical staining properties were correlated with the findings on radioimmunoassay.

Adult↗
PubMed1981

Postembedding staining of Brunner's gland with lectin-ferritin conjugates.

Postembedding staining of intracellular carbohydrates of rat Brunner's gland cells embedded in Epon and acrylamide was carried out with Ricinus communis agglutinin-ferritin, concanavalin A-ferritin, and wheat germ agglutinin-ferritin conjugates. Th Golgi vacuoles and mucous granules were stained with these conjugates. In each staining, the tissues embedded in acrylamide were stained more strongly than those embedded in Epon. The staining intensity of wheat germ agglutinin-ferritin was the strongest among the three conjugates and the staining intensity of Ricinus communis agglutinin-ferritin was stronger than that of concanavalin A-ferritin in both embedding methods. Free ferritin showed almost no binding to these structures and staining with the conjugates was inhibited by the addition of appropriate competitive sugars to the staining solutions. Osmium-postfixed tissues were not stained well with the conjugates. Washing of the sections with bovine serum albumin solution after staining was an essential step in the present method to reduce the nonspecific adsorption of the conjugates. The present method was very simple and had good reproducibility.

Animals↗
PubMed1980

Immunoradioautographic study of alpha-fetoprotein in hepatoma cells.

Trypsin treatment, which is frequently used in the field of immunocytochemistry to faciliate conjugated antibody penetration through the cell membrane, was applied for the immunoradiographic demonstration of alpha-fetoprotein in ascites hepatoma cells using 125I-labeled anti rat alpha-fetoprotein antibody. No significant number of silver grains were detectable in the group without trypsin treatment, while numerous silver grains were recognizable in the ascites hepatoma cells after trypsin treatment. This indicates that trypsin treatment is effective for the immunoradiographic demonstration of alpha-fetoprotein and contributes to the quantitative immunoradioautographic investigation.

Animals↗
PubMed1980

Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration.

The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13-1.27 h) was observed after the different modes of administration. The mean [AUC] 0 infinity after rectal administration of a suppository showed the minimum significant difference (p < 0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10-15% of body weight. The renal contribution (mean, 0.10-0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3-12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63-75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71-96% and 73-93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 microgram/ml after the final dose of a 50 mg q. i. d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08 +/- 0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.

Administration, Oral↗
PubMed1980

Studies of the action pattern of an alpha-amylase from Streptomyces praecox NA-273.

An alpha-amylase [EC 3.2.1.1] from Streptomyces praecox was purified and its characteristic action, the conversion of maltotriose (G3) to maltose (G2) without appreciable formation of glucose (G1), was investigated. Isoelectric focusing or the glycogen adsorption procedure was employed after chromatography. Isoelectric focusing showed that the enzyme preparation after chromatographic separation comprises three isozymes. The preparation from the glycogen adsorption procedure showed the highest specific activity of any preparation of this enzyme ever obtained. Product analysis with uniformly labeled G3 revealed that at a high concentration (18 mM) of G3, much more G2 is produced than G1 (the product ratio G2/G1 is over 20), while at a lower concentration (10 microM) the reaction mixture was composed of nearly equimolar amounts of glucose and maltose. Based on the product analysis of reducing end-labeled G3 in addition to the above findings, the following conversion mechanism is proposed: Streptomyces alpha-amylase catalyzes transglycosylation to produce maltotetraose (G4) as a transient product which is immediately degraded into two molecules of G2 by a subsequent hydrolytic reaction, i.e., two molecules of G3 are converted into three molecules of maltose without appreciable formation of glucose.

Amylases↗
PubMed1979

Quantitative study on anomeric forms of glucose produced by alpha-glucosidases.

Anomeric forms of glucose produced from phenyl alpha-maltoside, maltose, or phenyl alpha-glucoside have been determined quantitatively by simultaneous measurements of optical rotation and reducing power, for eight kinds of glucose-producing 1,4-alpha-glucosyl hydrolases, including glucose-forming amylase from human urine, and alpha-glucosidases from pig serum, honey bee, buckwheat seed, rice seed, sugar beet seed, flint corn seed, and brewer's yeast. All the eight enzymes studied were found to produce alpha-glucose exclusively.

Animals↗
PubMed1978

A study of the mechanism of action of Taka-amylase A1 on linear oligosaccharides by product analysis and computer simulation.

The action pattern and mechanism of the Taka-amylase A-catalyzed reaction were studied quantitatively and kinetically by product analysis, using a series of maltooligosaccharides from maltotriose (G3) to maltoheptaose (G7) labeled at the reducing end with 14C-glucose. A marked concentration dependency of the product distribution from the end-labeled oligosaccharides was found, Especially with G3 and G4 as substrates. The relative cleavage frequency at the first glycosidic bond counting from the nonreducing end of the substrate increases with increasing substrate concentration. Further product analyses with unlabeled and end-labeled G3 as substrates yielded the following findings: 1) Maltose is produced in much greater yield than glucose from unlabeled G3 at high concentration (73 mM). 2) Maltooligosaccharides higher than the starting substrate were found in the hydrolysate of labeled G3. 3) Nonreducing end-labeled maltose (G-G), which is a specific product of condensation, was found to amount to only about 4% of the total labeled maltose. Based on these findings, it was concluded that transglycosylation plays a significant role in the reaction at high concentrations of G3, although the contribution of condensation cannot be ignored. A new method for evaluating subsite affinities is proposed; it is based on the combination of the kinetic parameter (ko/Km) and the bond-cleavage distribution at a sufficiently low substrate concentration, where transglycosylation and condensation can be ignored. This method was applied to evaluate the subsite affinities of Taka-amylase A. Based on a reaction scheme which involves hydrolysis, transglycosylation and condensation, the time courses of the formation of various products were simulated, using the Runge-Kutta-Gill method. Good agreement with the experimental results was obtained.

Amylases↗
PubMed1977

Bacteriolysis by immobilized enzymes.

Bacteriolytic enzymes produced by Achromobacter lunatus were immobilized in collagen membrane. Intact bacteria such as Pseudomonas solanacearum, Xanthomonas oryzae, Staphylococcus aureus, and Pseudomonas aeruginosa were lyzed with the bacteriolytic enzyme-collagen membrane. Relative activity of the bacteriolytic enzyme-collagen membrane against Pseu. solanacearum was about 2% of that of native bacteriolytic enzymes. No difference in the optimum pH was observed between immobilized enzymes and native enzymes. The bacteriolytic enzymes in the collagen membrane were stable against sodium chloride which was an inhibitor of the native bacteriolytic enzymes. Xanthomonas oryzae and Pseu. aeruginosa were continuously lyzed by a reactor containing the rolled bacteriolytic enzyme-collagen membrane.

Alcaligenes↗