Metabolism of toremifene in the rat

Toremifene was labelled to a specific activity of about 20 microCi/mmol with tritium at positions 3 and 5 in the para-substituted phenyl ring. At these positions tritium is not eliminated within the metabolic pathways. A mixture of unlabelled and labelled toremifene (5 or 10 mg/kg, 5 microCi/mg) was given i.v. or p.o. to Sprague-Dawley rats. The elimination of radioactivity was followed up by collecting urine and feces daily for 13 days. The elimination of toremifene which was similar after p.o. and i.v. administration took place mainly in the feces. About 70% of the total radioactivity was eliminated within 13 days, of this amount more than 90% in the feces. All applied radioactivity could be detected in three separate fractions according to the oxidative state of the side chain when counted by Berthold TLC Linear Analyzer. Each fraction was further separated into single metabolites by TLC or HPLC. Altogether 9 metabolites were identified and almost all methanol-extractable components were identified. The main metabolic pathways in the rat were 4-hydroxylation and N-demethylation. The side chain was further oxidized to alcohols and carboxylic acids. Small amounts of unchanged toremifene were found in the feces both after p.o. and i.v. administration indicating biliary secretion.     

Regulation of S-adenosyl-L-methionine decarboxylase by 1-aminooxy-3-aminopropane: enzyme kinetics and effects on the enzyme activity in cultured cells

The kinetics of inactivation of adenosylmethionine decarboxylase of rat liver and of baby hamster kidney cells (BHK21/C31) by 1-aminooxy-3-aminopropane was studied. The apparent dissociation constants (Ki) for the hepatic and BHK21/C13 enzymes were 1.5 and 2.0 mM and the times of half-inactivation at infinite concentration of the inhibitor (tau 1/2) were 1.2 and 3.8 min, respectively. Treatment of BHK21/C13 with 0.5 mM 1-aminooxy-3-aminopropane prevented cell growth and depleted the cells of putrescine and spermidine within 1 day. The depletion of spermidine resulted in increased activity of S-adenosylmethionine decarboxylase which was due, at least partly, to the increase in the half-life of the enzyme activity. Because spermine levels were not significantly affected, it appears that spermidine is the principal feedback regulator of S-adenosylmethionine decarboxylase. So, 1-aminooxy-3-aminopropane is a very weak inhibitor of S-adenosylmethionine decarboxylase and the cellular effects can be correlated primarily with its inhibitory effects on ornithine decarboxylase and spermidine synthase. In cell-free systems, however, 1-aminooxy-3-aminopropane is likely to find use in unraveling the reaction mechanism of S-adenosylmethionine decarboxylase.     

Zooplankton in the Vasikkalampi pond, a warm water effluent recipient in Central Finland

Seasonal and vertical fluctuations of zooplankton species composition,biomass, and production were monitored by weekly sampling duringa two year period in one eutrophic pond in Central Finland.The study was one part of a more comprehensive study programto investigate the effects of warm water effluents from onesmall thermal power plant (35 MW) on the pond ecosystem. Becauseof the circulation of the pond water through the pumps in thepower plant the crustacean populations were very sparse in planktonduring the seasons the power plant was in operation (late Augustto May). During that time rotifers were dominant and some speciesreached very high densities (e.g., Keratella cochlearis s.l.ca. 15 000 ind. l^–1 in sping). In summer months Asplanchnapriodonta, Ceriodaphnia quadrangula, Bosmina longirostris, Mesocyclopsleuckarti and Thermocyclops oithonoides were dominant. A totalof 96 planktonic and meroplanktonic taxa were identified (26ciliates, 46 rotifers, 21 cladocerans and 3 copepods). The dryweight biomass of total zooplankton was 10 mg m^–3 in wintermonths, 10–100 mg m^–3 in spring and 300–1000mg m^–3 in summer. The total yearly production of zooplanktonwas 8552 mg dry wt m^–3 a^–1 in 1979 and 8440 mg drywt m^–3 a^–1 in 1980, from which the proportion ofrotifers was 33–39%, cladocerans 52–58% and copepods8.6 –9.4%. The winter production was 0.2–0.5% ofthe total yearly production, that of spring and autumn togetherwas 8.1–10.4% and the remainder (89–91%) was summerproduction.