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T Itami

Publications and source records attributed to T Itami.

At least 55 records · Page 3Linked to original sources
PubMed1984

[Studies on the pharmacological bases of fetal toxicity of drugs (VII). Enhancement effect of bacterial pyrogen on the fetal toxicity of salicylic acid].

We reported previously that the acute and fetal toxicities of aspirin (ASA) were enhanced by bacterial endotoxin (LPS). In order to clarify the mechanism of the enhancement by LPS, the effects of LPS on the toxicities of salicylic acid (SA), the main metabolite of ASA, were investigated in rats. The following results were obtained: 1) The acute toxicity of SA was significantly potentiated by LPS in male rats. The LD50 of SA with LPS was about one third of that of SA alone. 2) The increase of maternal body weight was inhibited significantly after administration of SA (383 mg/kg, p.o.) with LPS (20 micrograms/kg, i.v.), but not after administration of SA alone. 3) The fetal toxicity of SA including fetal death, resorption, growth retardation and skeletal variations was slightly observed in the dam receiving a single dose of SA on the 15th day of pregnancy, but it was markedly increased by LPS (20 micrograms/kg, i.v.). 4) The half-life period of SA in plasma was increased significantly by the co-administration of LPS in male rats after administration of ASA or SA. All of these phenomena in the rats given SA closely resembled the phenomena previously reported in the rats given ASA. These results suggest that SA might play a main role in the acute and fetal toxicities of ASA, and one of the mechanism of the enhancement effect by LPS on ASA-induced fetal toxicity might be related to the increase of SA concentration in the fetus.

Animals↗
PubMed1984

[Studies on the pharmacological bases of fetal toxicity of drugs. (VI) Teratogenic effects of trypan blue and related compounds in rats].

The teratogenicity of trypan blue and its related compounds was studied in Wistar rats and the following results were obtained: 1) o-Tolidine, 1-amino-8-naphthol-3, 6-disulfonic acid or 1-nitronaphthalene-3, 6-disulfonic acid was injected subcutaneously on day 7 of pregnancy (sperm = day 0). No fetotoxicity was observed in any group. 2) The main fractions, blue fraction (blue fr.) and red fraction (red fr.), were separated from commercial trypan blue (C-TB) by silica gel column chromatography. C-TB, blue fr. or red fr. was injected into pregnant rats subcutaneously on day 7 of pregnancy. The incidence of malformed fetuses after injection of blue fr. was higher than that of C-TB, and the types of malformations induced by C-TB and blue fr. were similar. However, no fetotoxicity was detected after injection of red fr. 3) Blue fr. or red fr. was injected into the exocoelom on day 11 of pregnancy. The incidence of malformed fetuses in the group injected with blue fr. (2.5 micrograms/embryo) was 39%, and the types of malformations were abnormal tail and vertebrae, which were also observed after injection of C-TB or blue fr. into pregnant rats. No significant teratogenic effect was observed after injection of red fr. From these data, it was concluded that the teratogenic effect of C-TB might be due to the blue fr., but not the red fr.

Abnormalities, Drug-Induced↗
PubMed1983

Studies on the pharmacological bases of fetal toxicity of drugs (IV). Effect of endotoxin and starvation on serum protein binding of salicylic acid in pregnant rats.

Our previous paper reported that the fetotoxic effects of aspirin (ASA) were enhanced by bacterial endotoxin (LPS), and the effects of ASA were attributed to its major metabolite, salicylic acid (SA), as indicated by high SA concentrations in fetus and placenta. In order to clarify the mechanisms of the enhancement by LPS, serum total protein, albumin and free fatty acid (FFA) levels and SA-binding capacity of serum protein were investigated in pregnant rats. The following results were obtained: 1) FFA levels increased steadily after day 16 of pregnancy, and SA-binding capacity of serum protein decreased gradually after day 18, as the pregnancy proceeded to full term. 2) LPS injection decreased total protein and albumin levels in normal and starved rats on day 15 of pregnancy. 3) Starvation and/or LPS injection potentiated the increase of FFA level and reduced significantly SA-binding capacity of serum protein in the rats on day 15 of pregnancy. 4) Serum protein showing low SA-binding capacity from LPS-treated rats recovered normal SA-binding capacity when FFA was removed from serum protein by charcoal treatment. These data suggested the decrease of the SA-protein binding in serum by the increased level of FFA, an inhibitor of the binding, and the decreased level of albumin as a possible mechanism for the potentiation of the fetotoxicities of ASA by LPS.

Animals↗
PubMed1983

[Studies on the Dutch rabbit for pyrogen test].

A study was conducted on Dutch rabbits to examine their applicability for the pyrogen test in comparison with the Japanese white rabbit which, conventionally, has been mainly used for the test in Japan. The following results were obtained. Adult Dutch rabbits, so small as to weight only about 60% of average adult weight of the Japanese white, showed a food consumption as low as 40% of that in the latter. None in the Dutch rabbit group suffered dislocation of the hip-joint during restraint on a neck stock while it was frequently encountered among Japanese white rabbits. The body temperature during restraint was unstable in infantile Dutch rabbits (7-8 weeks old)(, but stable in the young (14 weeks old) and in the adult (20-47 weeks old). Adult Dutch rabbits exhibited greater febrile responses to intravenously injected bacterial pyrogen (LPS) than infantile and young Dutch rabbits and adult Japanese white rabbits. A good linear regression was observed between the dose of LPS (0.01-0.1 microgram/kg, iv) and the febrile response in adult Dutch rabbits as well as in adult Japanese white rabbits. From these data, it is concluded that the Dutch rabbit has an advantage over the Japanese white for the pyrogen test in respect of febrile responsiveness and cost of rearing.

Age Factors↗
PubMed1982

[Studies on the pharmacological bases of fetal toxicity of drugs. (I). Relation of fetal toxicity and tissue concentration of acetylsalicylic acid with pyrogen in pregnant rats].

The mechanism for the enhancing effect of pyrogen (lipopolysaccharide, LPS) on the fetal toxicity of acetylsalicylic acid (ASA) was studied in pregnant rats. The lethality of ASA was significantly enhanced by LPS in male rats. The fetal toxicity of ASA including fetal death, resorption, growth retardation, and skeletal anomalies (wavy rib and asymmetry of sternebra) was slightly observed in the dams that received a single dose of ASA (125 to 500 mg/kg, p.o.) on the 15th day of gestation, but it was markedly increased by LPS (20 micrograms/kg, i.v.). The enhancement of the toxicity of ASA by LPS was also observed in the maternal body weight gain until term. The plasma concentrations of ASA and salicylic acid (SA), the major metabolite of ASA, were increased by LPS. The tissue concentrations of SA were also increased in the following order: placenta, brain, fetus, uterus, liver and kidney. The ATP levels of placenta and fetus were not influenced by ASA alone, but markedly decreased by both LPS and ASA.

Abnormalities, Drug-Induced↗
PubMed1980

Cardiovascular effect of "peritoneal dialysate-depressor-I", a short-active hypotensive phospholipid in dog peritoneal dialysate.

Cardiovascular action of "peritoneal dialysate-depressor-I" (PD.D-I), a short-acting hypotensive phospholipid occurring in dog peritoneal dialysate, was investigated. With an intravenous injection of PD.D-I into an anaesthetized rat, a sharp fall of arterial blood pressure was observed and the effects were dose dependent. The maximum hypotensive effect was about 60 mmHg and the minimum effective dose was approximately 35 micrograms/kg. Neither tachyphylaxis nor sensitization was observed. Even in conscious rats PD.D-I elicited hypotensive responses, though the effect was much weaker than that produced in anaesthetized rats. In spinal rats the hypotensive effects were also observed. In the tests on rats reserpinized or pretreated with antimuscarinic, antihistaminic, beta-adrenergic-blocking and ganglionic-blocking agents, the depressor effect of PD.D-I was not affected. PD.D-I elicited also hypotensive responses in anaesthetized cats, rabbits and guinea pigs in the same degree as those in anaesthetized rats. The relaxation of the peripheral blood vessels was observed in the test on perfused rabbit ear. The depressor factor showed no smooth muscle stimulating activity in isolated guinea pig ileum preparations. Judging from these findings, the hypotensive effect of PD.D-I is not ascribable to the central, sympathetic or parasympathetic nervous system but possibly to direct action on the peripheral vascular system.

Animals↗
PubMed1979

Occurrence of short-duration hypotensive phospholipid from dog peritoneal dialysate.

From the total lipid fraction of dog peritoneal dialysate after freeze drying and extraction, a hypotensive phospholipid was isolated through silicic acid, cellulose, and Sephadex LH-20 column chromatography in a pure grade; it showed a single spot on TLC. The purified hypotensive factor, designated as Peritoneal Dialysate Depressor-I, elicited potent depressor responses in anesthetized rats, and its threshold dose was approximately 35 microgram/kg. The material resisted proteases and 15-hydroxyprostanoate oxidoreductase. In mobility on TLC, the hypotensive factor was distinuishable from water-soluble hypotensive substances and also from depressor lipids. Judging from its behavior on TLC and column chromatography during the purification procedure, the hypotensive factor seems to be a choline-containing phospholipid and shows the general characteristics of hysolecithin, except for its potent hypotensive activity, and 2',7'-dichlorofluorescein on TLC. The molar ratio of phosphorusurated ones such as stearic and palmitic acids.

Animals↗
PubMed1979

Action of depressor-I, a hypotensive phospholipid from bovine brain, on systemic and arterial blood pressures of various species.

Effects of "Depressor-I" (D-I), a new hypotensive phospholipid obtained from bovine brain lipid fraction, on systemic arterial blood pressure were investigated. The hypotensive activity of D-I in urethane anaesthetized rats was dose dependent and tachyphylaxis and/or sensitization were not observed. Increments of the respiration and the heart rate were observed with sharp falls in blood pressures following intravenous administration of D-I, in simultaneous recordings in anaesthetized rats. D-I elicited hypotension in all species of animals examined, and the sensitivities to D-I were much the same, however, there were two types in patterns of duration on responses and the durations were also dose dependent. D-I exhibited depressor-responses even in conscious rats, though responses were much smaller compared with those seen in anaesthetized rats. In a comparison of anaesthetic agents in rats, the highest hypotensive activity of D-I was observed with pentobarbital anaesthesia, a moderate response was seen with alpha-chloralose and the least response was seen with urethane. In spinal rats or those pretreated with reserpine or antagonists, such as atropine, diphenhydramine, propranolol and hexamethonium, D-I also elicited hypotension. These results suggest that "Depressor-I" does not elicit the depressor action via the stimulation of the central and the autonomic nervous systems but rather by a direct action on peripheral blood vessels.

Anesthesia↗