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Effect of thioacetamide on rat liver regeneration. II. Nuclear RNA in mitosis.

The effect of thioacetamide on dividing cells of regenerating rat liver has been studied. Rats were given daily subcutaneous injections of thioacetamide as a 1 per cent solution at a dosage of 5 mg./100 gm. body weight for 7 to 10 days, subjected to partial hepatectomy, and sacrificed 28 to 31 hours later. Thioacetamide treatment results in striking increases in the nuclear ribonucleoproteins of the liver cell without affecting the mitotic rate during regeneration (14). During mitosis, RNA-containing particles were seen within the spindle and coating the contracted chromosomes from prophase through metaphase or early anaphase. At telophase, prior to the reconstruction of the nuclear membrane, fine RNA-containing granules appeared within the compact chromosomal groups. These coalesced to form nucleoli corresponding in number to the number of nucleolar organizer regions. The nuclei and nucleoli showed a rapid increase in size during the reconstruction period when compared with corresponding figures of the control liver samples. Electron micrographs of interphase nucleoli indicated a similar basic granular structure in both drug-treated and control animals. The question is raised as to whether the increased nucleolar material merely made visible some of the nucleolar-chromosomal associations that normally occur in mitosis, or whether thioacetamide directly affects the synthetic activity of the contracted mitotic chromosomes.

Amides↗

The chemical constitution of compounds which protect erythrocytes against freezing damage.

Eleven simple neutral water-miscible compounds were tested for protective action against freezing damage to human red blood cells. All the compounds penetrated the cells at room temperature without damage, but only four, N-substituted amides, were active. These results are considered together with previously published work on freezing protection by other low molecuar weight solutes. The affinity of the compounds for water is gauged in two independent ways, and correlates well with protective ability. The chemical constitutional factors responsible for high affinity for water are discussed. It appears that basic character is most important.

Amides↗

The schistosomicidal and toxic effects of some N-p-aminophenoxyalkylamides.

Several N-(omega-p-aminophenoxyalkyl)amides were active against Schistosoma mansoni in mice. One of the most effective, N-(5-p-aminophenoxypentyl)benzamide (M&B3002), acted more rapidly than lucanthone on adult worms but less rapidly than antimony potassium tartrate. It was inactive against immature worms. This compound and M&B2948A (N-(5-p-aminophenoxypentyl)phthalimide) were both active against S. mansoni in hamsters. In monkeys M&B2948A was inactive, whilst M&B3002 was not tested for therapeutic activity. Several of the compounds were examined for the production of visual impairment in cats. Although this property was not entirely absent, its incidence was very much lower in this amide series than among other omega-p-aminophenoxyalkyl derivatives not containing an amide group. M&B3002 and M&B2948A produced impairment of vision in only a small proportion of the large number of cats tested. The general toxicology of the two drugs was studied in several species, and also their absorption and excretion in mice and rats; this was to provide information for a clinical trial.

Amides↗