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S Awazu

Publications and source records attributed to S Awazu.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of adriamycin-induced lipid peroxidation.

Lipid peroxidation is known to be a mechanism for Adriamycin-induced toxicity. In the present study, two methods which detect fluorescent substances and high molecular weight protein aggregates in peroxidized membranes were applied to Adriamycin-induced lipid peroxidation in liver microsomes. A rat liver microsomal suspension containing an NADPH-generating system was incubated with Adriamycin. Thiobarbituric acid reactive substances (TBA-RS), formed during this incubation, were transferred from the microsomes to the medium. Fluorescent substances determined by the fluorescence emitted from both the microsomes themselves and the chloroform/methanol extracts of the microsomes, were found to be formed during this incubation. High molecular weight protein aggregates determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were also formed. Fluorescent substances and high molecular weight protein aggregates were found in microsomal membranes themselves and increased time dependently. These substances retained in membranes can be of great use to delineate the site of Adriamycin-induced lipid peroxidation in vitro and in vivo and to determine how this lipid peroxidation affects the membrane.

Animals↗
PubMed1992

Intestinal active absorption of sugar-conjugated compounds by glucose transport system: implication of improvement of poorly absorbable drugs.

The intestinal absorption of glucose- and galactose-conjugated compounds was studied in the everted sac of the rat small intestine. The absorption clearance of p-nitrophenyl beta-D-glucopyranoside (p-NPglc) at 250 microM in the mucosal side (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4), calculated by dividing the absorption rate by the drug concentration, was significantly decreased (0.476 +/- 0.036 microL/min/cm) in the presence of 1 mM phloridzin, an inhibitor of glucose transport, and in the absence of Na+, a cosubstrate of the glucose transport carrier (0.424 +/- 0.018 microL/min/cm). The absorption clearance of p-NPglc was decreased as its concentration increased. In the same experiment, the absorption clearance of p-nitrophenyl beta-D-galactopyranoside (1.99 +/- 0.23 microL/min/cm) was also significantly decreased in the presence of phloridzin and in the absence of Na+. However, the absorption clearance of p-nitrophenyl beta-D-mannopyranoside (0.811 +/- 0.013 microL/min/cm) was low and not significantly decreased in the presence of phloridzin (P greater than 0.1). Furthermore, the absorption clearance of beta-naphthyl beta-D-glucopyranoside and beta-naphthyl beta-D-galactopyranoside was also significantly decreased in the presence of phloridzin (P less than 0.001). These results indicated that the glucose and galactose moieties provided these compounds with a new route by way of the glucose transport carrier for intestinal absorption.

Animals↗
PubMed1992

Human urine deoxyribonuclease II (DNase II) isoenzymes: a novel immunoaffinity purification, biochemical multiplicity, genetic heterogeneity and broad distribution among tissues and body fluids.

Deoxyribonuclease II (DNase II) was purified from the urine of a 48-year-old male (a single individual) using a column chromatography series, including concanavalin A-agarose and an immunoaffinity column utilizing anti-human spleen DNase II antibody, and was then characterized. Based on the catalytic properties of the purified enzyme, we have devised a technique of isoelectric focusing by thin-layer polyacrylamide gel electrophoresis (IEF-PAGE) combined with a specific zymogram method, for investigating the possible molecular heterogeneity of human DNase II. DNase II in urine as well as the purified form was found to exist in multiple forms with different pI values separable by IEF-PAGE within a pH range of 5-7. Since sialidase treatment of the urine sample induced simplification of the isoenzyme patterns with diminishment of anodal bands, it was clear that the multiplicity of the enzyme was in part due to differences in the sialic acid content. On screening of DNase II isoenzyme patterns in urine samples from more than 200 Japanese individuals, only the common isoenzyme pattern was observed and no electrophoretic variations were detected. However, genetic studies of urinary enzyme activity and comparative studies on the activity in urine, semen and leukocytes from the same individuals suggest that the enzyme activity level of DNase II may be under genetic control. The enzyme was widely distributed in human tissues and showed high activities in secretory body fluids such as breast milk, saliva, semen and urine, and leukocyte lysates.

Body Fluids↗
PubMed1992

Fluorospectroscopic analysis of the fluorescent substances in peroxidized microsomes of rat liver.

The fluorescent substances formed in rat liver microsomes in the course of lipid peroxidation were investigated by fluorescence techniques. The fluorescence emitted from peroxidizing microsomes continuously increased as lipid peroxidation progressed, while the steady-state fluorescence anisotropy increased and then reached a plateau. A similar increase was observed in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in peroxidizing microsomes. The fluorescence from peroxidized microsomes consisted of at least three species having short, middle or long fluorescence lifetimes. The lifetimes and relative amplitudes of fluorescence were unaffected by the extent of lipid peroxidation. Both fluorescence of the chromolipids extracted and the proteins isolated from peroxidized microsomes had the same characteristics in fluorescence lifetimes as the fluorescence from whole peroxidized microsomes. Thus, these lipids and proteins appear to be the major biological substances responsible for the fluorescence emanating from whole peroxidized microsomes. Furthermore, fluorescent substances formed in microsomes seem to increase in quantity rather than change in quality as lipid peroxidation progresses.

Animals↗
PubMed1992

Differences in the enhancing effects of sodium caprate on colonic and jejunal drug absorption.

We examined the enhancing effect of sodium caprate (C10) on the jejunal absorption of a poorly absorbed drug, cefmetazole, in rats, in comparison with its colonic absorption (Pharm. Res. 5, 341-346, 1988). Jejunal absorption was significantly enhanced by C10, but to a smaller extent than colonic absorption. Membrane perturbation, caused by the interaction between C10 and membrane proteins or lipids, was shown to increase transcellular drug permeability, as reported in the colon. Paracellular permeabilities, obtained from the permeabilities of water-soluble nonelectrolytes of various molecular weights, showed a two-phase pattern against their free diffusion coefficients, suggesting the existence of at least two pore routes similar to those in the colon. C10 increased paracellular permeability in the colon but not in the jejunum. Impedance analysis and voltage clamp technique in the jejunum showed no significant effect of C10 on paracellular permeability, such as found in the colon. Accordingly, the difference in the effects of C10 on the jejunal and colonic absorption of cefmetazole was due mainly to the difference in its effects on the paracellular pathway.

Animals↗
PubMed1992

High molecular weight protein aggregates formed in the liver of the rat following large doses of paracetamol.

Paracetamol (200 and 500 mg kg-1) was given intraperitoneally to rats pretreated with 3-methylcholanthrene for 3 days. Glutamic oxalacetic acid transaminase (GOT) activity in plasma increased in rats receiving 500 mg kg-1 paracetamol. Plasma GOT activity was low at the dose of 200 mg kg-1, but the same dose to diethyl maleate pretreated rats increased the GOT activity. High mol. wt protein aggregates were found to be formed in liver homogenates and microsomes of rats which showed high plasma GOT activity, accompanied by depletion of hepatic glutathione. The formation of protein aggregates in the liver of rats following large doses of paracetamol suggests a contribution of lipid peroxidation to paracetamol-induced hepatotoxicity.

Acetaminophen↗
PubMed1992

Species and organ differences of sulphate conjugation of p-nitrophenol in liver and platelets.

Sulphate conjugation of p-nitrophenol (p-NP) in the liver and platelet cytosol of guinea pigs, rabbits and dogs were studied. The dependency of phenol sulphotransferase (PST) activity on p-NP concentration in the liver of guinea pigs and rabbits and in the platelets of guinea pigs were similar to that reported for the liver (Mizuma et al., J. Pharmacobio-Dyn., 6, 851 (1983)) and platelets (Nakamura et al., J. Pharm. Pharmacol., 42, 207 (1990)) of rats. There was one peak of PST activity on p-NP at the concentration of 1 to 10 microM, and the PST activity was increased again with an increase of p-NP concentration above the original concentration. On the other hand, a peak in PST activity on p-NP at the concentration of 1 to 10 microM was not observed in the platelets of rabbits and dogs. These results indicated species and organ differences in PST activity on p-NP in liver and platelets. The biphasic activities of the PST and p-NP in platelets and liver of rat and guinea pig were similar to that reported in humans (Reiter et al., Naunyn-Schmiedeberg's Arch. Pharmacol., 324, 140 (1983)).

Animals↗
PubMed1992

Thermal characteristics of poly (DL-lactic acid) microspheres containing neurotensin analogue.

The thermal characteristics of poly (DL-lactic acid) (DL-PLA) microspheres containing a hexapeptide (NA: H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt) with neurotensin activity were investigated. PLA microspheres with a drug content of 1.5-11.0% were prepared by a novel o/w (oil-in-water) solvent evaporation method. Both DL-PLA and NA were amorphous in form, and an increase in heat capacity at glass transition temperature (Tg) of the polymer was observed in DL-PLA microspheres containing NA. The Tg of DL-PLA (PLA2000 bulk) was 307.8 K, while Tg of microspheres containing NA (content 6.0%) shifted to 321.2 K. The Tg of PLA2000 microspheres was found to increase with an increase in the content of NA, and its increasing tendency reached a plateau at an NA content of greater than 6%. The apparent activation energy of glass transition of PLA2000 bulk and the microspheres was calculated to be 86.3 and 99.3 kcal/mol, respectively. As a result of the release test after storage at 4 degrees C and 40 degrees C for 1 month, nearly the same release profiles of NA from PLA2000 microspheres were found. The release rate of NA after the initial release became slow after storage at 45 degrees C for 1 month. This may be attributed mainly to a decrease in surface area caused by the formation of agglomerates of PLA2000 microspheres under conditions near Tg.

Drug Storage↗
PubMed1979

A case of mesenteric cyst diagnosed by ultrasound examination and a review of Japanese literatures.

Mesenteric cyst is relatively rare, and its diagnosis is difficult. We carried out an ultrasound examination on a 6-year-old boy who showed intestinal obstruction. This examination revealed an abdominal mass, and he was diagnosed as mesenteric cyst. Later it was confirmed by operation. The histopathological examination revealed that it was a lymphangioma. A review was also carried out on 288 cases of mesenteric cyst in Japan.

Child↗
PubMed1978

Correlation between in vitro and in vivo drug metabolism rate: oxidation of ethoxybenzamide in rat.

In vitro and in vivo correlations of the microsomal oxidation of drugs were examined, using ethoxybenzamide as a model drug. Ethoxybenzamide disappearance time course from rat plasma in vivo was analyzed by a two-compartment model assuming a Michaelis-Menten type elimination process. Ethoxybenazmide oxidation in vitro was measured by the appearance rate of salicylamide in rat liver microsomal suspension. Parameters obtained were Vmax = 3.46 and 3.77 mumoles/min/kg body weight and Km = 0.378 and 0.192 mM, in vitro and in vivo, respectively.

Animals↗
PubMed1978

Meckel's diverticulum. Investigation of 600 patients in Japanese literature.

A total of 600 cases, comprising 4 of our cases and 596 others in Japan, was analyzed, and the diagnosis of Meckel's diverticulum was made in only 34 of them. The rate of diagnosis was 5.7 per cent, which is very low. The most common complication of this disease was intestinal obstruction, the second most common was intussusception, the third was inflammation, and the fourth was rectal bleeding. Ectopic tissue, present in ninety-three patients, consisted of ectopic gastric mucosa in fifty-eight. 99mTc-P scanning was performed on fifteen patients. In twelve of them ectopic gastric mucosa was observed. However, it was not found in three, all of whom had false-positive scans.

Adolescent↗