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Biomedical subjects

M Ema

Publications and source records attributed to M Ema.

At least 91 records · Page 5Linked to original sources

Teratology study of Tween 60 in rats.

The teratogenicity of Tween 60 was studied in Wistar rats. Pregnant rats were given Tween 60 at a dose of 0, 0.1, 1.0 or 10% in the diet from day 7 to day 14 of pregnancy. Daily intakes of Tween 60 were 99 mg/kg for the 0.1% group, 960 mg/kg for the 1.0% group and 7693 mg/kg for the 10% group. No change induced by Tween 60 was detected in the number, sex ratio and body weight of live fetuses. External, skeletal and internal examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that Tween 60 has no harmful effects on the prenatal development of the rat offspring at doses employed in the present study.

Animals↗

Malformations in rat fetuses induced by trypan blue.

Malformations of fetuses obtained from Wistar rat dams treated with trypan blue during gestation were studied. Fetuses were examined on day 20 of gestation. One hundred and twenty-seven fetuses showed abnormalities of the external features, skeleton and internal organs, separately or in combination. External malformations were found in 108 fetuses. The most frequent external malformation was anomaly of tail. Spina bifida, club foot, exencephaly and anal atresia were also observed frequently. Skeletal malformations were detected in 48 fetuses. Deformity of vertebrae in the lumbar, sacral and/or caudal regions was found in 46 fetuses. Internal malformations were observed in 27 fetuses. Anomaly of heart and/or great vessels, hydrocephaly and micro- or anophthalmia were observed frequently. About 90% of the fetuses with skeletal malformations also showed some external malformations. In contrast, about 48% of the fetuses with internal malformations also had some external malformations. These results suggest that, for teratological study, internal examination is more important in detecting malformations of fetuses than skeletal examination.

Abnormalities, Drug-Induced↗

[A cylindrical thermistor probe for experiments on suppositories in rabbits].

A cylindrical thermistor probe with a rubber disk stopper, which is beneficial for inserting a suppository into the rectum of rabbits without removal of the probe from the rectum, was developed. It is possible to measure body temperature continuously by using this probe in an experiment to assess the effects of a suppository on the body temperature of rabbits. After insertion of a suppository, leakage of the melted suppository from the rectum was not observed. No differences between this thermistor probe and an ordinary thermistor probe in the ability of the probe to detect the febrile response of rabbits injected with a bacterial pyrogen were observed. From these results, it could be concluded that this newly improved cylindrical thermistor probe is suitable for studying the effect of suppositories on the body temperature of rabbits.

Animals↗

Antipyretic effect of indomethacin suppository in rabbits.

We have designed a thermistor rectal probe thermometer for measuring the antipyretic activity of suppositories. Using this thermistor probe, we tested the antipyretic effect of an indomethacin suppository in comparison with oral and intravenous administrations in rabbits (male, 2.5-2.9 kg). The rectal temperature of normal rabbits remained unchanged after rectal and intravenous administration of indomethacin, 25 mg/body and 10 mg/kg, respectively. The antipyretic effect was tested in febrile rabbits injected with bacterial pyrogen, lipopolysaccharide (LPS) 0.2 microgram/kg (i.v.). The dose-dependent antipyretic activities were observed in febrile rabbits administered with indomethacin by rectal (6.3-23.7 mg/body), intravenous (2.5-10 mg/kg) and oral (2.5-20 mg/kg) routes. When indomethacin was administered simultaneously or 1 h after LPS, the most potent antipyretic effect was observed in the case of rectal administration and the weakest effect was observed in that of oral administration. These data indicate that the rectal administration of drugs can produce a potent antipyretic activity, not inferior to that of the intravenous injection.

Administration, Oral↗

Antipyretic mechanism of indomethacin in rabbits.

The mechanism of the antipyretic effect of indomethacin (IM) on fever induced by bacterial pyrogen (LPS, 0.2 microgram/kg, i.v.), leukocytic pyrogen (LP, 2 ml/kg, i.v.) and 2,4-dinitrophenol (DNP, 20 mg/kg, i.m.) in male adult rabbits was studied. In plasma, the biological half lives of IM in normal and LPS-injected rabbits were estimated to be 24 and 21 min in the early phase and 72 and 51 min in the late phase, respectively. A potent antipyretic effect was observed with intravenous injection of IM in LPS- and LP-induced fevers, but not in DNP-induced fever. The antipyretic effect was also observed with intracisternal injection of indomethacin at doses of 0.025 and 0.013 mg/kg. The activity of endogenous pyrogen in serum after LPS injection was not suppressed by the injection of IM (10 mg/kg, i.v.). The production of LP by leukocytes in vitro was not inhibited by IM (10 micrograms/ml). In our previous report, it was ascertained that the rectal temperature of normal rabbits remained unchanged after intravenous injection of IM. These results suggest that indomethacin may inhibit only the pyretic processes in the central nervous system.

2,4-Dinitrophenol↗

[Thermistor probe for testing an antipyretic suppository in rabbits].

The thermistor probe for estimating the effects of an antipyretic suppository after its administration into the rectum of the rabbit was studied. A thermistor probe with three rubber disk stoppers was confirmed to be able to prevent the leakage of drugs from the rectum of a rabbit restrained in a neck stock. By using this newly devised thermistor probe or the usual thermistor probe without a stopper, the febrile response was determined in rabbits injected with bacterial pyrogen. There was no difference in the ability to detect rectal temperature between the two thermistor probes. From these results, it could be concluded that this newly devised thermistor prove was useful in studying the effects of antipyretic suppositories in rabbits.

Animals↗

Liver function in moderate obesity--study in 534 moderately obese subjects among 4613 male company employees.

The influence of moderate obesity on the liver was assessed in 4613 male company employees including 534 moderately obese subjects (30-50 percent overweight). Serum levels of transaminases and gammaglutamyl transferase activities were significantly higher in moderately obese male non-drinkers than in non-obese non-drinkers. Twenty-four percent of male non-drinkers with moderate obesity had abnormal levels of sGPT and 47 percent of moderately obese male non-drinkers had significant hepatic steatosis as assessed by computed tomography. Although most previous studies on this subject were concerned with morbid obesity accompanying only those of more than 50 percent overweight or those who required surgery, the results of this study clearly indicate that moderately obese subjects also have frequent liver dysfunction.

Alanine Transaminase↗

[Studies on the pharmacological bases of fetal toxicity of drugs. (V) Effect of different administration routes of trypan blue in rats].

The teratogenicity of trypan blue (TB) after both maternal and intrauterine administrations was studied in Wistar rats, and the following results were obtained: 1) The teratogenic dose of TB by maternal subcutaneous injection was found to be greater than 50 mg/kg, and the critical period was until day 10 of pregnancy (sperm = day 0). No teratogenicity was detected by oral administration of 250 mg/kg TB. 2) TB (250 micrograms/uterine horn) was injected into the uterine cavity on day 4 or 6 of pregnancy. An increase of intrauterine death without malformations was observed in both TB-treated groups. 3) TB was injected into the exocoelom. The incidences of malformed fetuses were 53% in the group injected with 2.5 micrograms/embryo TB on day 10 and 32% and 57% in the groups injected with TB at 1.0 and 2.5 micrograms/embryo on day 11, respectively. An increase of intrauterine death was observed in these groups. Types of malformations observed in these groups were abnormal tail, spina bifida and deformity of vertebrae, and were almost similar to those observed by maternal subcutaneous injection of TB. 4) A trace of TB was found microscopically in the frozen section of embryo after both subcutaneous and intraexocoelom injections of TB. These results suggest that TB acts directly on embryos to produce malformations.

Abnormalities, Drug-Induced↗

[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↗

[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↗

[Studies on the pharmacological bases of fetal toxicity of drugs. III. Fetal toxicity of potassium nitrate in 2 generations of rats].

The fetal toxicity of potassium nitrate (KNO3) used widely as a food additive was studied in Wistar rats. The pregnant rats were fed a diet containing 2.5, 0.5 or 0.1% of KNO3 from day 7 to 14 of pregnancy. Neither maternal nor fetal toxicity including external malformations were observed at term in any group. After spontaneous delivery, the offspring were reared until 13 weeks after birth. No harmful effects were detected in any group. The female offspring (F1) of all groups were mated with the male (F1) of the same group. Good reproductive performances were shown in all groups. The pregnant rats were fed the same diet, which their mothers (F0) had been fed, from day 7 to 14 of pregnancy. Various types of malformations such as exencephaly, cleft lip and palate, polydactyly and micro- or anophthalmia were observed in 6 of 133 fetuses and 7 of 63 newborns from dams treated with 2.5% KNO3, but no external malformations were observed in other groups. The male offspring (F2) of the treated groups showed slow growth until 13 weeks after birth. These results suggest that a dose of 2.5% KNO3 is toxic to the F2 generation, but not to the F1 generation.

Abnormalities, Drug-Induced↗

[Studies on the pharmacological bases of fetal toxicity of drugs. (II). Effect of trypan blue on the pregnant rats and their offspring].

We performed studies on the mechanisms for the teratogenicity of trypan blue (TB) that is known as a potent teratogenic dye in rodents. TB was administered to Wistar rats at various doses and at different stages of gestation. Teratogenicity and embryolethality were observed by a single (50 and 250 mg/kg) subcutaneous injection and three (25 and 50 mg/kg) subcutaneous injections of TB daily from day 7 of pregnancy. The incidences of malformations in groups given 50 and 250 mg/kg on day 7 were 12 and 59%, respectively. Most of the fetuses with external malformations were accompanied with skeletal and/or internal anomalies. The types of frequently occurring malformations were as follows: exencephaly, spina bifida, tail anomaly, vertebral deformity, hydrocephaly and heart anomaly. Fetal toxicity was decreased after treatment with the mixture of TB and normal rat serum. The serum level of TB in pregnant rats increased to 308 micrograms/ml at one hour after subcutaneous treatment with TB 50 mg/kg and decreased rapidly, but remained at 58 micrograms/ml 72 hours later. Lower serum levels of TB were observed in pregnant rats given TB with serum. No fetotoxic effects of serum from pregnant rats treated with TB were observed in recipient rats given the serum on day 7, 8 and 9 of pregnancy.

Abnormalities, Drug-Induced↗