-Teriparatide, a therapeutic agent for osteoporosis, has been reported to increase the incidences of bone neoplasms such as osteosarcoma when administered subcutaneously to Fischer 344 (F344) rats for a long term, but its non-carcinogenic dose level following 2-year daily administration has not been established. Here we report detailed studies on the carcinogenicity of teriparatide following longterm administration. When teriparatide was administered subcutaneously to male and female SpragueDawley (SD) rats daily for 2 years, the incidence of osteosarcoma was increased at 13.6 μg/kg/day. The non-carcinogenic dose level was 4.5 μg/kg/day for both males and females. The development of osteosarcoma in SD rats depends on the dose level of, and treatment duration with, teriparatide. Responses of the bones to teriparatide were similar between F344 and SD rats in many aspects. These results suggested that the carcinogenic potential of teriparatide in SD rats is essentially the same as in F344 rats.

Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) was prepared from soybean lecithin and L-serine by a transphosphatidylation reaction, and its effect on age-related memory impairment was evaluated in rats by the Morris water maze test. Continuous oral administration of SB-tPS (60 mg x kg(-1) x d(-1) for 60 d) to male aged rats (24-25 mo) significantly improved performance in the water maze escape test (P < 0.01 vs. control aged rats) similar to bovine brain cortex-derived phosphatidylserine, which restores cognitive function in patients with senile dementia. SB-tPS also increased acetylcholine release and the Na(+), K(+)-ATPase activity of the synaptosomes prepared from these aged rats to the level in young rats. The nootropic actions of SB-tPS in the present study can be partly explained by the changes in these biochemical activities.

SummarySoybean transphosphatidylated phosphatidylserine (SB -t PS) was prepared from soybean phosphatidylcholine by transphos phatidylation using phospholipase D, and the fatty acids composition and pharmacological properties were compared with those of bovine brain cortex-derived phosphatidylserine (BC-PS) which was reported to im prove cognitive disorders of senile dementia patients by oral administra tion (300mg/day). The molecular species of SB-tPS are rich in linoleic and palmitic acids whereas those of BC-PS are stearic and oleic acids. Despite the differences in fatty acid composition, SB-tPS displayed signifi cant activities on the increase in brain glucose concentrations in mice (79 mg/kg, i.v.) and the restoration of scopolamine-induced amnesia in rats (60mg/kg, i.p.) as did BC-PS. These results suggest the possibility that SB-tPS may prevent and/or improve senile dementia by oral administra tion.

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Abstract:The aim of this study was to collect data on immunological parameters from Wistar Hannover rats at 8, 10, 19, and 32 weeks of age. Low leukocyte parameter cell counts, serum globulin concentration, and T, B, and NK lymphocyte counts in peripheral blood at each time point; low T, B, and NK splenocyte counts; and high, or tendencies toward high, thymocyte counts at 10 weeks of age were noted in females when compared with males. KLH-specific antibody production increased gradually with age in both sexes. The immunological data noted for leukocyte parameters, the serum globulin concentration, and immunophenotyping (peripheral blood, spleen, and thymus) relating to chronological changes and sex differences may be useful in assessing drug-related immunotoxicity in this strain.