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Biomedical subjects

O Wada

Publications and source records attributed to O Wada.

At least 127 records · Page 7Linked to original sources
PubMed1987

Detection of Trp-P-1 and Trp-P-2, carcinogenic tryptophan pyrolysis products, in dialysis fluid of patients with uremia.

In order to estimate the exposure levels of mutagenic and carcinogenic heterocyclic amines in humans, we developed a high-performance liquid chromatography method to detect 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in dialysis fluid of patients with uremia. Using this methods, dialysis fluid of 12 patients who had received hemodialysis treatment or continuous ambulatory peritoneal dialysis was examined. Trp-P-1 was detected in dialysate of all uremic patients (727 +/- 282 pmoles, n = 12). In patients who had been treated with continuous ambulatory peritoneal dialysis, the average amount of Trp-P-1 found in whole dialysate (6 l) per day was 710 +/- 203 pmoles (mean +/- S.D., n = 8). Moreover, Trp-P-2 could be detected in 5 out of 12 patients (206 +/- 85 pmoles, n = 5). These results indicate that patients with uremia are actually exposed to carcinogenic tryptophan pyrolysis products. The average exposure level of Trp-P-1 in uremic patients apparently exceeded 710 pmoles (150 ng) per day.

Carbolines↗
PubMed1987

Inhibitory effects of tryptophan pyrolysis products on human platelet aggregation through inhibition of prostaglandin endoperoxide synthetase.

To determine the effects of the carcinogenic heterocyclic amines on the stimulus-reaction system in cells, the effects of several such amines, including 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), on human platelet aggregation and of Trp-P-1 and Trp-P-2 on human polymorphonuclear leucocyte aggregation were investigated. Of the carcinogens studied, only Trp-P-1 and Trp-P-2 had potent inhibitory effects on human platelet aggregation induced by sodium arachidonate. The concentrations of Trp-P-1 and Trp-P-2 causing 50% inhibition of human platelet aggregation induced by sodium arachidonate were 15 and 25 microM, respectively. The heterocyclic amines examined had no significant effects on human polymorphonuclear leucocyte aggregation. Moreover, radiochemical studies of arachidonate metabolism showed that Trp-P-1 and Trp-P-2 inhibited, in a dose-dependent manner, the formation of cyclooxygenase products in platelets induced by sodium arachidonate. These results indicate that Trp-P-1 and Trp-P-2 have potent inhibitory effects on prostaglandin endoperoxide synthetase in the stimulus-reaction system of human platelets.

Adult↗
PubMed1987

Separation of biologically active chromium complex from cow colostrum.

By a procedure based on ion-exchange chromatography, five chromium-containing fractions were separated from the ethanol extract (50-90%) of cows' colostrum which should provide infant with all or most of the chromium needed in available form. Three of the fractions are anionic (A-1, A-2 and A-3) and two are cationic (C-1 and C-2). Two major fractions, A-1 and A-3, comprise together about 77% of the total chromium recovered in the effluent after ion-exchange chromatography and C-1 and C-2 comprise together only about 21%. Approximate molecular weight was determined by the Sephadex gel chromatography to be 1,500 for A-1 and C-2 and 2,000 for C-1. A-3 was eluted from the Sephadex gel column at the elution position corresponding to that of inorganic trivalent chromium. Among five fractions, A-1 shows glucose tolerance factor (GTF) activity as measured by the stimulation of [U-14C] glucose oxidation to 14CO2 in rat epididymal adipocytes. A-1 stimulates glucose oxidation at chromium concentration as low as 100 pg/ml only when it is incubated with insulin. These findings suggest that A-1 fraction separated from cow milk contains a low-molecular-weight, chromium complex which plays a role in glucose metabolism in close relation with the action of insulin.

Adipose Tissue↗
PubMed1987

Introduction of new indices into continuous avoidance test--a trial to detect the effects of sodium chloride and mannitol on avoidance behavior.

A personal computer was introduced in conditioned lever-press avoidance experiment in Sidman situation. Experimental data were analyzed with both classic indices such as response rate and shock rate and new indices introduced in this experiment. New indices include sum of squares of shock-shock intervals, mean of shock-response time and number of shock-response time less then 5 sec. Results obtained in diazepam-treated mice were consistent with those reported previously by the classic method. In mannitol-treated mice, significant changes of the avoidance behavior could be detected by both the classic index and our new indices. By the new indices other than classic indices, the effect of administration with sodium chloride on the avoidance behavior could be detected, whereas the classic indices could not detect the effect. Though the meanings of these indices i physiological and toxicological aspects should be appreciated in future study, the experimental system reported in this paper might be applicable in the toxicological research to detect the effect of administration with various substances on the avoidance behavior.

Animals↗
PubMed1986

Presence of 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) in dialysate from patients with uremia.

MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline), a carcinogenic heterocyclic amine, was found to be present in dialysis fluid of 8 patients with uremia, but not in fresh dialysis fluid before dialysis treatment. Concentrations of MeIQx in dialysates ranged from 14 to 32 pM. The mean absolute contents of MeIQx in dialysates (6 to 40 liters) was 334 p mole. These results indicate that the carcinogenic heterocyclic amine is present in the plasma of all patients with uremia.

Adult↗
PubMed1986

Miconazole inhibition of platelet aggregation by inhibiting cyclooxygenase.

Platelet dysfunction was found in rabbits to which a dose of miconazole nitrate (1.6 mg/kg body wt) therapeutic for human subjects had been given intravenously. The present experiments were conducted to elucidate the mechanism of inhibitory effects of miconazole on platelet function. After administration of a single dose of miconazole, rabbit platelet aggregation induced by collagen and sodium arachidonate was inhibited significantly for approximately 24 hr. On the other hand, hypertriglycemia, one of the major side effects of this drug, was not seen during 2 days of observations, nor were any other outstanding manifestations observed. In in vitro experiments, miconazole nitrate (10 microM) also significantly inhibited rabbit and human platelet aggregation (P less than 0.01). Biochemical analyses revealed that the stimulant-induced formation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), metabolites via cyclooxygenase, was inhibited by miconazole nitrate in both human and rabbit platelets in vitro. PGE2 production was decreased dose-dependently with the increase of miconazole concentration (10 to 100 microM), and the decrease was in parallel with a decrease of TXB2 production. In addition, malondialdehyde (MDA) production of human and rabbit platelets induced by exogenous arachidonate and collagen was also inhibited significantly by miconazole. Chromatographic studies showed that the amount of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), a metabolite via lipoxygenase, was increased markedly in accordance with the miconazole-induced decrease of TXB2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation in both human and rabbit platelets. These results indicate that miconazole nitrate inhibits platelet cyclooxygenase, without affecting the stimulant-induced release of arachidonic acid from platelet phospholipids. Use of this drug in the treatment of systemic fungal infection appears to be increasing. Careful attention should be paid to the inhibitory effects of miconazole on platelet function, especially in the case of intravenous treatment.

Adenosine Diphosphate↗
PubMed1986

Cadmium stimulates glucose metabolism in rat adipocytes.

Cd2+ caused an increase in CO2 formation from glucose in rat adipocytes. The apparent Km value for glucose was 2.02 mM for control condition, with Cd2+, and with insulin. Cd2+ stimulates glucose metabolism even though specific diffusion of glucose is blocked. A possible site effected by Cd2+ is discussed.

Adipose Tissue↗
PubMed1986

[Toxicity assessments of chemical substances using primary culture of rat hepatocytes].

A primary hepatocyte culture was used as a model system to assess the toxicity of various chemical substances. Chemical substances tested in this experiment included 14 kinds of organic solvents, arsenic acid and N-nitrosodiumethylamine, most of which are known as hepatotoxic materials. Enzyme (GPT and LDH) leakage and albumin secreted from the hepatocytes to culture medium were measured to evaluate the cell damage after exposure to the chemical substances at various concentrations for 3 d. Cell counts and protein contents before and after exposure to the chemical substances were also measured during the course of these experiments. The extent of LDH leakage from hepatocytes was parallel to that of GPT leakage after exposure to the chemicals. Albumin secreted from the hepatocytes in the culture medium evidently decreased at concentrations of the chemicals which increased the enzyme leakage. Viable cell counts were significantly decreased by chemicals that increased the enzyme leakage, although the cell protein contents were not significantly affected. The minimum concentration of the chemicals at which enzyme leakage from hepatocytes was significantly increased was defined as the lowest toxic concentration (TCL0). Judging from TCL0 values, the degree of toxicity in these chemicals seems to be almost identical to the degree of in vivo hepatotoxicity reported previously. We, furthermore, observed that there is a positive correlation (r = 0.780, p less than 0.01) between PT50 calculated by the LD50 value reported previously and -Log magnitude of TCL0.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1985

Effect of age on the modification of rat plasma lipids by fish and soybean oil diets.

The effects of sardine and soybean oils on plasma lipids have been studied in young and aged rats. Plasma cholesterol and bile acids of aged rats fed on a sardine oil diet decreased to a greater degree than those of young rats. Cholesterol, bile acids and phospholipids of the soybean oil diet group decreased only in aged rats. Increases in plasma eicosapentaenoic (sardine) and linoleic (soybean) acid levels of aged rats were observed to be greater than those of young rats. These results indicate that the age enhances the effects of fish and soybean oils on plasma lipids by suppressing their characteristic fatty acid metabolism.

Aging↗
PubMed1985

Age-associated changes in rat plasma lipids, platelet fatty acids and prostacyclin release.

The effect of age on plasma lipids, platelet fatty acids and prostacyclin release was studied in the rat. The contents of arachidonic acid, cholesterol, bile acids and free fatty acids in the plasma of aged rats (15 months old) were higher than those of young rats (3 months old). No significant differences in fatty acid composition of platelet lipids and release of prostacyclin from aortas between young and aged rats were observed. The data suggest that plasma lipids may play a more important role in the development of cardiovascular disease with increasing age than prostaglandins do.

Aging↗
PubMed1984

Inhibition of carrageenan edema formation by organotin compounds.

The effects of a single p.o. dose of 0.3-10 mg/kg of organotin compounds such as dibutyltin dichloride (Bu2SnCl2) and triphenyltin chloride (Ph3SnCl) on the development of edema after subplantar injection of 0.5 mg of carrageenan in 0.05 ml of pyrogen-free saline were examined as compared with those of hydrocortisone. Bu2SnCl2, Ph3SnCl and hydrocortisone did not significantly inhibit the development of the first phase of edema at any dose level, but produced more than 90, 70 and 90% inhibition of the second phase, respectively, at a dose of 10 mg/kg 1 hr before the irritant. Moreover, these inhibitions of the second phase were dose-dependent.

Animals↗
PubMed1984

Inhibition of neutrophil chemotaxis by organotin compounds.

Organotin compounds such as Bu2SnCl2, Bu3SnCl and Ph3SnCl suppressed significantly not only chemotactic response of neutrophils to stimulation by the chemoattractant fMet-Leu-Phe but also phospholipase activity in situ as measured by the release of [1-14C] arachidonic acid previously incorporated into phospholipids. Moreover, these suppressions were dose dependent and a parallelism was found between dose-dependent inhibition of chemotaxis and that of arachidonate release. These results suggest that the chemotactic response is controlled by the activation of phospholipase activity in neutrophils, and that the inhibitory effects of these organotin compounds on chemotactic response reflect the blockage of phospholipase activation system regulated by phosphorylation of lipomodulin.

Animals↗
PubMed1984

Cadmium-induced stimulation of lipogenesis from glucose in rat adipocytes.

Exposure of adipocytes of rats to CdCl2 caused acceleration of [3-3H]glucose incorporation into lipid maximally at 500 microM in Krebs-Ringer bicarbonate buffer, pH 7.4, containing 0.2% albumin. T.l.c. of the lipids extracted from adipocytes showed that Cd2+ increased labelling of di- and tri-[14C]acylglycerols predominantly. With increasing concentrations of glucose the apparent Km value was not affected by Cd2+, but the V value was increased, similarly to the effect of insulin. In the presence of insulin, Cd2+ (5 microM) exerted a consistent additive effect with a stimulatory effect of insulin on lipogenesis at all concentrations of insulin tested (5-50 mu units/ml). The stimulation was observed at a high concentration of glucose, suggesting that Cd2+ accelerated intracellular metabolism of glucose, mimicking insulin. However, although Zn2+ and Mn2+ stimulated the transport at a rate similar to that observed with insulin (200 mu units/ml), Cd2+ had no stimulating effect on the membrane transport of 3-O-methylglucose. The biological potency of Cd2+ and the insulin-like effects of Zn2+, both of which metals belong to the same group in the Periodic Table, are similar towards glucose metabolism, but quite different towards glucose transport.

3-O-Methylglucose↗
PubMed1984

Species difference in sensitivity to the diabetogenic action of triphenyltin hydroxide.

The sensitivity to the diabetogenic action of triphenyltin hydroxide (TPTOH) was investigated in 5 species of experimental animals. A single oral administration of TPTOH produced marked hyperglycemia and triglyceridemia in rabbits and hamsters, but no evidence of diabetes was found in mice, rats and guinea-pigs. No morphological abnormality was observed in islet tissue from TPTOH-treated hamsters.

Animals↗