The influence of diazepam treatment following prolonged ethanol administration was toxicologically examined in rhesus monkeys and rats. In the monkey, ethanol was intragastrically administered through a chronically implanted catheter by programmed infusions at doses of 1.5 g/kg 4 times daily every 6 hours over a period of 5 or 10 weeks and followed by intragastric administration of diazepam 4 mg/kg twice a day for 5 weeks. In the rat, ethanol was administered by gavage at doses of 8 g/kg once a day or 4g/kg twice a day for 5 weeks after which diazepam 300 mg/kg was intragastrically administered once daily for 5 weeks. In the monkey, ethanol produced such toxic changes as hypertriglyceridaemia, fatty metamorphosis of the hepatocytes associated with megamitochondria, proliferation of smooth endoplasmic reticulum and vacuolation in the hepatocytes, and gastritis. Diazepam did not aggravate but mostly alleviated these changes. In the rat, on the contrary, the serum GPT level slightly elevated due to the ethanol administration, and remained at the elevated level with the diazepam treatment in contrast with the complete recovery with non-treatment for 5 weeks after the ethanol administration. However, such changes as increase of fat droplets in the hepatocytes and the triglyceride concentration in the liver which had been developed by ethanol administration recovered during the diazepam treatment period. In spite of the recovery, the elevation of the serum GPT level being remained by diazepam may indicate possible influence of diazepam on the liver function when the drug is administered after prolonged administration of ethanol.
Allethrin had a stimulating action on spontaneous discharges in the cockroach sixth abdominal ganglion superfused with an insect saline solution. This action at a low concentration (5x10-8M) of allethrin was abolished by either of d-tubocurarine, hexamethonium or atropine at 5x10-4M. It was also abolished by the treatment of ganglia with hemicholinium-3 or by low-calcium-high magnesium insect saline solution. However, treatment of these blocked ganglia with allethrin at more than 5x10-7M overcame the block, producing increased spontaneous activity. Allethrin had no effect on insect cholinesterase activity. These results may suggest that the stimulating action at a low concentration of allethrin may be mediated by the release of ACh from cholinergic terminals in ganglia.
Spontaneous neoplastic and non-neoplastic lesions in 98 male and 100 female Slc: Wistar rats, which have been widely used in Japan for toxicological studies, were examined. As spontaneous tumors, the most frequent tumors in males were testicular interstitial cell tumors, followed by tumors of the hematopoietic organs, adrenal gland, thyroid gland, preputial gland, pituitary gland, liver and mammary gland. Those in females were tumors of the pituitary gland, mammary gland, hematopoietic organs, uterus and thyroid gland. The organ distribution and histological types of spontaneous tumors observed in Slc: Wistar rats were very similar to those in F-344/DuCrj rats, although the incidences of some tumors differed slightly in the two strains. Various non-neoplastic lesions were also observed in the heart, kidney, liver and many other organs. These results should be useful in evaluating the results of toxicological and carcinogenic studies on this strain of rat.
Time-dependent changes of microscopic localization of intravenously administered colloidal carbon particles were studied in mouse lymph nodes. Carbon particles were preferentially trapped by postcapillary venules (PCV) immediately after injection, and migrated easily outside of PCV either through intercellular space of the PCV endothelium or by phagocytic process during the 1 hr after injection. Particles were thereafter up-taken by pericytes and macrophages around PCV during the 24 hr, and consequently distributed throughout the cortex and medulla. Finally, they migrated to the medullary lymphatic sinuses, and phagocytosed by endothelial cells. Redistribution process of particles via the lymphatic sinuses from the regional lymph was observed during 30 minutes or 10 to 14 days after injection in different lymph nodes.
Subacute toxicity of STO was carried out using Wistar rats. STO was administered intravenously at dose levels of 12.5, 50.0 and 200.0 mg/kg for 35 days. No influence on general symptom, body weight, food and water consumption and urinalysis were observed. In 200.0 mg/kg group, the hematological examination revealed anemia corresponding to the histological findings of the bone marrow. Biochemical analysis displayed the significant increase and/or decrease of enzyme values in 200.0 mg/kg group. Morphology showed the swelling, vacuolization and granuloma of the spleen, hepatic granuloma, the increase of reticulum cells and granuloma in the bone marrow. Embolism and thrombus were also found in the pulmonaly and tail veins probably due to an artifact caused by the i. v. injection. The toxicity of the STO were observed only in 200.0 mg/kg group of both sexes and any remarkable change other than physical effects were found in other groups under the above dosage. Accordingly, the maximal no-effect level of the STO in Wistar rats was considered to be 50.0 mg/kg.