The effect of Pluronic F-127 (PF-127), a surfactant polyol, on the loading of fura 2/AM into smooth muscle cells isolated from guinea pig taenia coli was investigated. The presence of PF-127 during the loading of fura 2 acetoxymethyl ester (fura 2/AM), an intracelluler Ca indicator, occasionally increased the incorporation of the dye into the cells. However, long time loading (over approximately 60 min) in the presence of PF-127 decreased the incorporation of fura 2. When the extracellular medium obtained from cells treated with DFP, then incubated with fura 2/AM in the presence of PF-127 was analyzed with excitation spectra, the fluorescence peaks shifted to longer wave lengths by addition of EGTA. However, the peak of the ektracellular medium obtained from cells treated with DFP, then incubated without PF-127, did not shift. These results show that PF-127 affects the membranous permeability of the dye in single smooth muscle cells, permititing fura 2 hydrolyzed in the cytoplasm to leak out through the membrane.
Hypoprothrombinemic changes were compared in rats fed various vitamin K-deficient diets. Changes such as prolongation of prothrombin time and activated partial thromboplastin time, decrease in plasma levels of prothrombin and clotting factor VII, and increase in plasma descarboxyprothrombin, appeared in rats maintained on vitamin K-deficient diet, but in rats on ordinary diet (vitamin K-sufficient diet). As the development of hypoprothrombinemia was not significanthly different among animals fed various vitamin K-deficient diets, the blood coagulation parameters were concluded to be regulated only by the vitamin K level. Following the development of hypoprothrombinemia, hemorrhaging in various organs was detected in vitamin K-deficient rats, with strain differences in the severity of hemorrhage ; Fischer and Wistar strains were more sensitive than the Sprague Dawley strain. Administration of a beta-lactam antibiotic, latamoxef (LMOX), to vitamin K-deficient rats led to enhancement of the hypoprothrombinemic conditions, but LMOX-associated changes in plasma enzyme levels were not detected.
The age-related incidence of spontaneously occuring neoplastic and non-neoplastic lesions in untreated F-344/Jcl rats, used as controls in carcinogenicity testing, were studied from the histological examination of tissues from 469 males and 354 females. The incidence of spontaneous tumors was 83.2% in the males and 71.2% in the females. The most common neoplasms were leukemia (males : 24.3%, females : 24.0%), pituitary adenoma (males : 16.0%, females : 45.2%), pheochromocytoma (males : 14.7% females : 7.3%, testicular interstitial cell tumor (males : 79.1%), and uterine endometrial stromal polyp(females : 16.4%). The incidence of other tumors of almost all the organs and/or tissues was low. Non-neoplastic lesions generally increased with advancing age of the animals.
This study was designed to establish a procedure for detecting the phototoxicity of drugs in an animal model. Experimental conditions in relation to intensity distribution of ultraviolet-A (UVA), duration of irradiation, and suitable region for irradiation were investigated. One black light gave a wide constant-energy region when the distance from the light source to the irradiation area was 15 cm. The intensity distribution of a bank of 10 black lights formed a pattern like the contour map of a truncated cone in the irradiation area. In phototoxic studies, Balb/c strain mice were orally administered chlorpromazine and nalidixic acid, clinically known as photosensitizers, and were immediately exposed to UVA irradiation. The optimal irradiation time was 4 hours at an energy of 20 Joules/cm2, which with a high frequency caused erythema on the surface of the ears in the central area, which received about 1.5 mW/sec·cm2, but no reaction occurred in the surrounding area (0.5-0.8 mW/sec·cm2). These results indicate that it is important to select a suitable irradiation area and sufficient intensity of irradiation in order to determine whether a drug has phototoxic potential.
The effect of D-galactosamine (GalN) on the blood clearance of <99m>Tc-phytate (<99m>Tc-P) in rats was examined, and the blood clearance test of <99m>Tc-P was compared with the cases of serum transaminase and bilirubin test. Serum transaminase and bilirubin levels in rats increased dosedependantly after GalN administration. The disappearance rate of <99m>Tc-P from blood decreased with the increase in dose of GalN and with the passage of time after the GalN administration. Changes of the blood clearance of <99m>Tc-P after GalN treatment in rats may be influenced by the disorder in the hepatocytes and the alteration of the liver reticuloendothelial system phagocytic function. The blood clearance test of <99m>Tc-P in rats showed a sensitive reaction for the acute hepatic dysfunction induced by GalN equally to or higher than the serum transaminase and bilirubin test.
The mutagenicity of protamine sulfate has been clarified based on chromosomal aberration of cultured chinese hamster lung cells (cell line) in direct and metabolic activation methods and microbial mutagenesis (Ames test). In chromosomal aberration test, protamine sulfate caused cytotoxicity in the high doses (2500 and 5000 μg/ml) in the presence of rat liver homogenates (S-9). But very negligible or no cytotoxicity occurred in direct method at high dose (5000 μg/ml). Structural aberration of chromosome was not occurred in either of the methods. In microbial mutagenesis study, protamine sulfate did not show any cytotoxicity to microbes up to the dose of 5000 μg per plate. Furthermore, it did not have any effect in microbes like mutagens or like some toxic agent. The study reveals that protamine sulfate is not mutagen.