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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 865 records · Page 48Linked to original sources
PubMed1985

[Study on toxicity of halopredone acetate. (I) Acute toxicity study in mice and rats].

Since halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injections because of its long-lasting activity in the synovial bursa, its acute toxicity was compared with that of triamsinolone acetonide (TA) and methylprednisolone acetate (MPA). The test animals were Jcl: ICR mice and Jcl: Wistar rats, and drugs were administered orally, intraperitoneally and subcutaneously. The LD50 values of THS-201 both in mice and rats were estimated more than 5000 mg/kg at each route, and these are for above larger than those of TA or MPA. Moreover, in oral and subcutaneous administration of THS-201, no severe toxic signs were observed either in mice or in rats. In intraperitoneal injection, a few of mice and rats died after showing several clinical signs and suppression of body weight gain, and their autopsy revealed atrophy of thymus, spleen and adrenal, induction of infection and hemorrhage in digestive tract. On the other hand, the mice and rats administered TA or MPA revealed the severe toxic signs such as loss of hair gloss, marked emaciation, decrease in spontaneous movement, anemia, bloated face, decrease or suppression of body weight gain, atrophy of thymus, spleen and adrenal, severe induction of infection and lesions in digestive tracts. Accordingly, it is concluded that the acute toxicity of THS-201 in mice and rats was lower than that of TA or MPA.

Administration, Oral↗
PubMed1985

[Peri- and postnatal study on halopredone acetate in rats].

A peri- and postnatal study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. Pregnant rats were treated subcutaneously in doses of 0.05, 0.4, 3.2 and 25.6 mg/kg/day, from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal development of offsprings was observed. The results obtained from the present study were as follows. No influences of THS-201 administration were observed on gestation, delivery and lactation of dams. THS-201 administration did not have any influences on viability and development, various functions such as reflex response, learning and reproductive performance of F1 generation, and further on development of F2 generation. Therefore, it was concluded that the non-effect dose of THS-201 for the reproduction of dams and development of F1 generation was 25.6 mg/kg/day.

Animals↗
PubMed1985

[Study on toxicity of halopredone acetate. (II). Subacute toxicity study in rats].

Halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injection because of its long-lasting activity in the synovial bursa. Subacute toxicity study was carried out on THS-201 by using Jcl: Wistar rats. THS-201 was subcutaneously administered to the rat in doses of 0.1, 0.5, 2.5 and 12.5 mg/kg/day, with the periods for administration and recovery being 3 and 2 months, respectively. Methylprednisolone acetate (MPA) was used for the positive control in dose of 0.5 mg/kg/day. In the group of THS-201 12.5 mg/kg, the below findings were observed: thinning of lumbar hair, swelling of injection site, suppression in body weight gain and decrease of food consumption. The lesions to lymphatic system were indicated by the examinations of peripheral blood, autopsy and histopathology. Slight changes in erythrocytic and biochemical values were seen, and foreign body granuloma was observed in injected subcutis. These findings, exception for lesion of injection site, were almost recovered after the 2 month-recovery period. In the group of THS-201 2.5 mg/kg, some of the changes were noted slightly. In the groups of THS-201 0.5 and 0.1 mg/kg, any toxic changes attributable to THS-201 were not observed. On the other hand, in the group of MPA 0.5 mg/kg, similar findings noted in THS-201 12.5 mg/kg group were observed, but these changes were recovered almost completely at the end of the 2 month-recovery period. It was concluded that the non-toxic dose and the defined toxic dose of THS-201 in this study were 0.5 and 2.5 mg/kg/day, respectively.

Animals↗
PubMed1985

[Study on toxicity of halopredone acetate. (III). Chronic toxicity study in rats].

Chronic toxicity study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. THS-201 was subcutaneously administered to the rat in doses of 0.02, 0.1, 0.5 and 2.5 mg/kg/day, with the periods for administration and recovery being 12 and 2 months, respectively. In the group of THS-201 2.5 mg/kg, the below findings were observed: thinning of lumbar hair, suppression in body weight gain, decrease of food consumption in both sexes and decrease of water consumption in male. The lesions to lymphatic system were indicated by the examinations of hemogram, organ weight and histopathology. A few changes in urinary and biochemical values were seen, and foreign body granuloma was observed in the injected subcutis. After 2 month-recovery period, above-mentioned findings almost disappeared. In the group of THS-201 0.5 mg/kg, some of the changes were noted slightly and disappeared after the recovery period. In the groups of THS-201 0.1 and 0.02 mg/kg, any toxic changes attributable to THS-201 were not observed. It was concluded that the non-toxic dose and the defined toxic dose of THS-201 in this study were 0.1 and 0.5 mg/kg/day, respectively.

Animals↗
PubMed1985

[Fertility study on halopredone acetate in rats].

A fertility study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. Male rats were treated subcutaneously for 63 days before mating and throughout mating, and female rats were treated subcutaneously for 14 days before mating and until day 7 of gestation, in doses of 0.04, 0.2, 1.0 and 5.0 mg/kg/day. Male and female rats in the same dose were mated. All of the pregnant rats were killed on day 20 of gestation and their fetuses were examined morphologically. The results obtained from the present study were as follows. A decrease in body weight gain was observed in male rats of 1.0 and 5.0 mg/kg groups, compared to the vehicle control group. In female rats of 5.0 mg/kg group, a decrease in body weight gain during gestation period was observed. However, no influences attributable to THS 201 administration were observed on the fertility and fetal development. These results indicated that the non-effect dose of THS-201 for the fertility of rats and fetal development was 5.0 mg/kg/day.

Animals↗
PubMed1985

[Teratogenicity study on halopredone acetate in rats].

A teratogenicity study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. Pregnant rats were treated subcutaneously in doses of 0.1, 0.5, 2.5 and 12.5 mg/kg/day, from day 7 to day 17 of gestation. Two-thirds of pregnant rats were killed on day 20 of gestation to examine the development of fetuses, and remaining rats were allowed to litter naturally in order to investigate the postnatal development of offspring. The results obtained from the present study were as follows. During the gestation and lactation periods, there occurred a decrease in the maternal body weight gain in 2.5 and 12.5 mg/kg groups. No influences of THS-201 administration were observed on gestation, delivery and lactation of dams. No external, visceral and skeletal anomalies attributable to THS-201 were observed in the fetuses. THS-201 administration did not have any influences on viability and development, various functions such as reflex response, learning and reproductive performance of F1 generation, and further on development of F2 generation. Therefore, it was concluded that the non-effect dose of THS-201 for the reproduction of dams and development of F1 generation was 12.5 mg/kg/day.

Abnormalities, Drug-Induced↗
PubMed1985

[Serum and prostatic tissue concentration of ceftizoxime (CZX) after intravenous administration in cases of benign prostatic hypertrophy].

One gram of ceftizoxime (CZX) was administrated before transurethral resection in 38 cases of benign prostatic hypertrophy. Then the serum and tissue concentration of CZX was measured, and compared with the sensitivity of CZX to the bacteria separated from the urine of inpatients. The concentration of CZX in prostatic tissue was higher than the MIC80 for E. coli for 16.7 hr, for Klebsiella for 18.7 hr, for Proteus for 14.7 hr and for Serratia for 8.86 hr. Therefore, CZX was considered to be an effective drug against bacterial prostatitis.

Aged↗
PubMed1985

The therapeutic effects of orally administered 5'-deoxy-5-fluorouridine, 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil on experimental murine tumors.

The antitumor effects of three 5-fluorouracil-related compounds, 5'-deoxy-5-fluorouridine (5'-DFUR), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-fluorouracil (5-FU) itself, on several experimental murine tumors were compared after oral administration. 5'-DFUR showed strong antitumor activity against the solid type of four kinds of tumors tested with a wide range of effective doses, and also showed moderate antitumor activity against three kinds of solid tumors with a narrow range of effective doses. 5'-DFUR was effective against a few kinds of ascites tumors. In general, the antitumor activity of FT-207 was not very strong, with narrow ranges of effective doses under the present conditions. 5-FU showed strong toxicity but at lower doses its antitumor effectiveness was almost the same as that of FT-207. When the doses were divided into three and the divided dose was given orally three times a day for five consecutive days to mice bearing L1210 leukemia, this modality (with any of the three drugs) enhanced the ILS of the mice by two to three times in the case of the ascites type but not the solid type of L1210. The chemotherapeutic index in oral treatment of the solid type of tumors was higher for 5'-DFUR than for FT-207 or 5-FU. The minimum lethal doses in oral administration for five consecutive days were about 3, 1.5 and 0.5 mmol/kg/day for 5'-DFUR, FT-207 and 5-FU, respectively. In conclusion, 5'-DFUR appeared to have stronger antitumor activity and less toxicity than FT-207 and 5-FU, and it is therefore expected to be clinically useful.

Animals↗
PubMed1985

Scanning electron microscope study on the biodegradation of IOL and suturing materials.

The biodegradation of the IOLs (27 cases: mainly prepupillary lens with pupillary fixation, irido-capsular and angle supported lens and a J loop lens for posterior chamber lens) and suturing materials of four cases have been studied by Scanning Electron Microscope (SEM). The longest duration in the eye was 7.5 years and the shortest 0.3 year. The materials used for optics were PMMA with the exception of one case of glass. The materials for haptics were Nylon 6, Isot.PP, PMMA, PVDF, Polyimid and Pt-Ir. The suturing materials were Nylon 6 and Isot.PP. Nylon 6 degraded in the eye and Isot.PP degraded in the corneal tissue. But no biodegradation was observed in Isot.PP, PMMA, PVDF and Pt-Ir in the eye. In our investigations, biodegradation has some relationship to age (over 50 years old), duration (within 7.5 years) and inflammation of the eye, but ultimately biodegradation will depend on the individual situation. Degradation occurs most easily in the curved portion of Nylon 6.

Age Factors↗
PubMed1985

Effect of forphenicinol, a small molecular immunomodifier, in combination with cyclophosphamide on growth of and immunity to syngeneic murine tumors.

Forphenicinol (FPL) is a low molecular immunomodifier derived from forphenicine, a microbial product found by Umezawa and co-workers. We studied the antitumor effect of FPL, cyclophosphamide (CY), and the combination of the two on several syngeneic murine tumors. The tumors used were mammary carcinoma, L1210 leukemia, B16 melanoma, Lewis lung carcinoma, and glioblastoma. A single ip injection of CY on Day 1 followed by eight consecutive daily oral doses of FPL beginning 6 days after tumor inoculation showed strong cooperation in curing syngeneic mammary carcinoma inoculated intradermally in C3H/HeN mice, most mice being cured of the tumor by the combination therapy and subsequently having acquired strong specific immunity. Treatment with FPL alone (either pre- or post-treatment) also significantly inhibited the growth of the mammary tumor. FPL and CY also showed cooperation in inhibiting the growth of L1210 leukemia transplanted intradermally into CDF1 (BALB/c X DBA/2) mice and markedly prolonged the survival time but FPL treatment alone had no effect. The FPL-CY treatment also affected Lewis lung carcinoma and glioblastoma in syngeneic C57BL/6 mice and produced therapeutic synergism. FPL alone significantly inhibited the growth of B16 melanoma in C57BL/6 mice as well as the syngeneic mammary carcinoma in C3H/HeN mice. These findings suggest that oral administration of FPL in combination with chemotherapeutic agents can be used for treating cancer without causing toxicity, because of the synergistic efficacy of the combination.

Adjuvants, Immunologic↗
PubMed1985

[Sinus histiocytosis in the lymph nodes of breast cancer patients having undergone extensive radical mastectomy].

Sinus histiocytosis in the regional lymph nodes of 45 patients with breast cancer who had undergone extended radical mastectomy was studied by histological examination of 2,294 resected lymph nodes. Sinus histiocytosis was divided into three grades, marked, moderate, and mild to negative, by Ohmori's classification. The results indicated that: 1) sinus histiocytosis correlates fairly well with clinical stage, especially with the n-factor, and 2) the degree of sinus histiocytosis shows little difference between three groups of regional lymph nodes. The authors concluded that sinus histiocytosis dominates the prognosis and represents some aspect of a reticuloendothelial response of the whole body to carcinoma.

Breast Neoplasms↗