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Biomedical subjects

M Teranishi

Publications and source records attributed to M Teranishi.

At least 37 records · Page 2Linked to original sources

Age-related changes in the susceptibility to clofibric acid, a hypolipidemic agent, of male rat liver.

Age-related changes in the susceptibility to clofibric acid were investigated in male F344 rats of 8, 52, and 117 weeks old. Hepatomegaly, decrease of serum total cholesterol and triglyceride, increase of the total cytochrome P-450 contents, induction of the activities of microsomal omega-hydroxylation and peroxisomal beta-oxidation, proliferation of smooth endoplasmic reticulum and peroxisomes were detected in 8- and 52-week-old rats. In 117-week-old rats clofibric acid treatment resulted in decrease of serum total cholesterol, elevation of the activities of microsomal and peroxisomal enzymes, and slight proliferation of peroxisomes. These results suggest that the susceptibility of the male F344 rat liver to clofibric acid decreases in 117-week-old rats, though the effect is still recognizable.

Administration, Oral↗

Age-related changes in thyroid lesions and function in F344/DuCrj rats.

Age-related thyroid changes, such as those in weight, histology, morphometry, and hormonal concentrations were evaluated in 460 male and 460 female F344 rats from 9 to 109 weeks of age. The absolute weight of the thyroid increased with age in both sexes, but the relative weight was unaffected by age. Ectopic thymus and ultimobranchial cyst were observed in rats of both sexes from 9 to 109 weeks of age. The incidence of both congenital anomalies decreased with age. The incidence of follicular cyst, which was first observed in rats at 20 weeks of age, increased at 109 weeks. Hyperdistention of the follicle with infiltration of macrophages in the lumen and deposition of brown pigments in the cytoplasm of epithelial cells were observed in a few rats at 59 weeks of age. These follicular lesions were found in 29% of the males and 7% of the females at 109 weeks. The first thyroid tumor was seen at 59 weeks of age. In 109-week-old rats, 5% of males had follicular tumors, and 18% of males and 10% of females had C-cell tumors. At 82 weeks of age, the follicular area and the area of the follicular lumen increased, and the height of follicular epithelial cells decreased. Serum T3, T4 and TSH concentrations decreased with age and were significantly reduced at 82 weeks. These results suggest that in F344 male rats the thyroid structural and functional changes occurred with age, and thyroid function decreased after 82 weeks of age.

Aging↗

Male reproductive toxicity study of nitrazepam in rats.

The main focus of this study is the optimal administration period concerning toxic effects on male fertility in rats. To assess functional and morphological changes induced in the testis by nitrazepam, male rats were administered the drug at doses of 0, 20, 40 or 80 mg/kg during pre-mating periods of 2, 4 or 9 weeks and then the 2 weeks of mating. At the end of the administration period the animals were sacrificed and sperm number, motility, abnormalities and histopathological changes in the testis were examined. Decreases in testis weight, epididymis weight, number of sperm in the testis and sperm motility were observed in the 40 and 80 mg/kg sections of the 2, 4 and 9 week pre-mating treated groups. Mating with untreated females revealed no adverse effects on copulation rate in any group; however, a remarkable decrease in pregnancy rate was noted in the 80 mg/kg section of the 2, 4 and 9 week treated groups. On histological examination, various degrees of localized necrosis in the seminiferous epithelium and Leydig cell hyperplasia were observed in the testis. No clear changes were observed in the 20 mg/kg section of the 2 week pre-mating administration group, but at the 4 week time point, necrosis of spermatogenic cells began to appear. The primary morphological event was evident in spermatocytes with necrosis of the cytoplasm observed from 4 weeks after administration of nitrazepam, although sperm motility and sperm head counts were unaffected. From these findings, examination of sperm characteristics and histopathological changes in the testis are important parameters for evaluation of drugs inducing testicular damage. We conclude that a 4 week administration period is sufficient to detect effects of nitrazepam on male fertility.

Animals↗

Vascular mineralization in the monkey brain.

Mineralization of various degrees was found in the brains of 79 (59%) of 134 cynomolgus monkeys (Macaca fascicularis). There was no age dependency in the incidence or severity, nor were there any abnormalities in growth, weight gain, or neurologic signs, although a slight sex difference was observed. The lesions, which were basophilic and intensely positive for periodic acid-Schiff or von Kossa stain, occurred in the vascular walls of the globus pallidus in two types: globoid bodies with prominent concentric lamellar structures in and around the arteriolar and venular wall (type A) and fine granules in the media of small or medium-sized arteries (type B). Electron microscopic examination revealed dense deposits in the degenerated media of small or medium-sized arteries or the thickened walls of the arterioles. X-ray microanalysis demonstrated the presence of calcium, phosphorus, iron, zinc, magnesium, and aluminum.

Animals↗

Comparative study of goitrogenic actions of 3-substituted 1, 2, 4-triazoles in rats.

Antithyroid actions of 3-amino-1, 2, 4-triazole (ATZ), 3-mercapto-1, 2, 4-triazole (MTZ) and 3-nitro-1, 2, 4-triazole (NTZ), which are substituents on the 3-position of 1, 2, 4-triazole (TZ), and those of the parental compound, were compared in rats. After administration of either ATZ, MTZ, or NTZ, the thyroids of rats were enlarged with decreasing of colloid content and a proliferation of the follicular epithelia. The serum concentration of 3, 5, 3'-triiodothyronine and thyroxine decreased, while that of thyroid-stimulating hormone increased. ATZ, MTZ, and NTZ inhibited thyroid peroxidase activity both in vivo and in vitro. These antithyroid actions were the most remarkable in case of MTZ and were the least in case of NTZ. TZ had no effect on the thyroid function in vivo and in vitro. The results of Lineweaver-Burk analysis on the effect to lactoperoxidase activity indicated that ATZ, MTZ, and NTZ showed competitive inhibition. These results suggest that both MTZ and NTZ have goitrogenic effects on the thyroid through antiperoxidase action, such as ATZ. Thus, the 3rd carbon position of TZ is thought to be important for induction of goiter in rats. A comparison of the relationship between substituent on the 3-position of TZ and antithyroid activity shows that a mercapto moiety has more potent antithyroid action than an amino and a nitro moiety. It is concluded that the differences in antithyroid activity of TZ derivatives depend on the potency of the substituents.

Animals↗

A case of intracytoplasmic edema of follicular epithelial cells in rat thyroid.

Hydropic change of follicular epithelial cells in the thyroid was observed in a female Fischer 344 rat. Microscopically follicular epithelial cells were characterized by edematous swelling with weakly eosinophilic and homogeneous cytoplasm. The cytoplasm was negative for periodic acid-Schiff reaction, and thyroxine- and thyroglobulin-immunohistochemical reactions. Electron-microscopically, a small amount of amorphous substance was noted in remarkably dilated rough-surfaced endoplasmic reticulum (r-ER), and slight regressive changes of cytoplasmic organella were also observed. These morphological changes may indicate that focal intracytoplasmic edema was occurred in r-ER, and that the change belonged to hydropic degeneration of the thyroid follicular cells in the thyroid.

Animals↗

Spontaneous globoid mineralization in the cerebellum of rats.

Cerebellar globoid mineralization in two rats was examined by light and electron microscopy, and by X-ray microanalysis. The mineralization was round to oval in shape; it varied in size and was positive for the periodic acid-Schiff and von Kossa reactions. Ultrastructurally, a concentric lamellar structure was prominent in moderately electron-dense depositions. Elemental analysis revealed the presence of large amounts of calcium and phosphorus, and small amounts of zinc, potassium and aluminum.

Animals↗

Radioimmunoassay for the determination of 2-methoxyestriol concentration in plasma of pregnant women.

A specific assay method has been developed for the determination of 2-methoxyestriol in plasma of pregnant women. The quantitation was achieved by radioimmunoassay after extraction of the plasma with ethyl acetate and purification on a Sephadex LH-20 column. In order to obtain the immunogen for 2-methoxyestriol, 6-oxo-2-methoxyestriol was converted to its 6-(O-carboxymethyl)oxime derivative. The derivative was then coupled to bovine serum albumin by the mixed anhydride method, and rabbits were immunized with this conjugate. The antiserum obtained was partially purified by affinity chromatography on estrone 17-(O-carboxymethyl)oxime-aminohexyl Sepharose conjugate to eliminate the cross-reactive antibodies. Plasma 2-methoxyestriol concentrations in pregnancy were estimated to be mean values of 41.1 pg/ml (12th-14th week), 85.3 pg/ml (27th-29th week), and 97.5 pg/ml (37th-41st week).

Cross Reactions↗

Studies on cardiotonic agents. V. Synthesis of 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying various 5-membered heterocyclic rings at the 4-position.

A series of 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying various 5-membered heterocycles at the 4-position was synthesized and examined for cardiotonic activity in anesthesized dogs. The (4-oxo-2-thioxo-3-imidazolindinyl)amino derivatives showed the most potent inotropic activity. Marked loss of activity was observed in the 2,4-dihydro-3-thioxo-3H-1,2,4-triazolyl, the 2,4-dihydro-3-oxo-3H-pyrazolyl and the (2,3-dihydro-2-thioxo-3H-1,3,4-thiadiazol-5-yl)amino derivatives. The synthesis and structure-activity relationships are discussed.

Animals↗

Intratumoral induction of tumour necrosis factor by systemic administration of Bordetella pertussis vaccine.

Intratumoral induction of tumour necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as compared with that by the agent OK-432 was investigated in mice. Two hours after such administration tumour tissues tested were resected from the mice, homogenised, and the TNF activities in the homogenate were assayed using a L-929 fibroblast assay. Intravenous injection of BPV into mice bearing the MM46 carcinoma resulted in a greater concentration of TNF in the tumour homogenate than in the serum. With OK-432, however, there was a greater concentration of TNF in the serum than in the tumour homogenates. A high level of intratumoral TNF induction by BPV was also observed in mice bearing Meth A fibrosarcoma or Lewis lung carcinoma. The therapeutic effect against the Meth A fibrosarcoma was in parallel with the intratumoral TNF activity. Intratumoral TNF activity is therefore believed to be a good index of therapeutic effect.

Animals↗

Studies on cardiotonic agents. III. Synthesis of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives.

A series of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives was synthesized and examined for cardiotonic activity in anesthetized dogs. Alkylation of the 2-imidazolidinone (1) afforded the N-alkylated products, while alkylation of the 2-imidazolidinethione (12) afforded the S-alkylated derivatives accompanied with a small quantity of the N-alkylated products. The N-alkylated derivatives showed generally potent activity, and the S-alkylated ones exhibited weak activity. Insertion of an alkyl group between the piperidine and the imidazolidinone moiety generally resulted in a fall in activity.

Animals↗

Studies on cardiotonic agents. IV. Synthesis of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying substituted hydantoin and 2-thiohydantoin rings.

A series of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying substituted hydantoin and 2-thiohydantoin rings was synthesized and examined for cardiotonic activity in anesthetized dogs. Introduction of isopropyl and sec-butyl group at the 5-position of the hydantoin and thiohydantoin rings led to potent inotropic activity. Effects of insertion of an alkyl chain between the piperidine and the hydantoin rings were also examined. The structural requirements necessary for optimal cardiotonic activity within the series were investigated.

Animals↗

Increase in calf production by the transfer of bisected bovine embryos.

A total of 132 embryos were recovered from 17 superovulated donor cows 7 d after estrus. Seventy-four embryos were selected and assigned to 2 treatment groups. The number of whole embryos that were directly transferred (Group A) and bisected (Group B) were 44 and 30 embryos, respectively. Sixty demi-embryos were produced from 30 morulae to blastocyst-stage embryos that were bisected. One hundred-three embryos, including whole and demi-embryos without zonae pellucidae, were nonsurgically transferred. Only one whole or demi-embryo was transferred to each recipients. The pregnancy rate for whole embryos (A) was 63.6% (28/44), while for demi-embryos (B) it was 74.6% (44/59). There was no significant difference between the pregnancy rates of whole embryos (A) and bisected embryos (B) transferred 7 d after estrus. Forty-three calves including the 14 sets of identical twins were obtained from 30 original embryos (143.3%) using the embryo bisection technique.

Animals↗