Reference database of the main physiological parameters in Sprague-Dawley rats from 6 to 32 months.

A reference database comprising body weight gain, exploratory activity, hot plate response, serum biochemistry, haematology, organ weight (%) and a complete anatomopathological study containing non-neoplastic and neoplastic lesions over 1200 Sprague-Dawley rats from 6 to 32 months is described. Comparisons between age and sex were analysed.

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts.

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity.

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity(AU)

Application of empirical design methodologies to the study of the influence of reaction conditions and N-alpha-protecting group structure on the enzymatic X-Phe-Leu-NH(2) dipeptide synthesis in buffer/dimethylformamide solvents systems.

The influence of five different N-terminal protecting groups (For, Ac, Boc, Z, and Fmoc) and reaction conditions (temperature and dimethylformamide content) on the alpha-chymotrypsin-catalyzed synthesis of the dipeptide derivative X-Phe-Leu-NH(2) was studied. Groups such as For, Ac, Boc, and Z always rendered good peptide yields (82% to 85%) at low reaction temperatures and DMF concentrations, which depended on the N-alpha protection choice. Boc and Z were the most reactive N-alpha groups and, in addition, the most suitable for peptide synthesis. On the other hand, the use of empirical design methodologies allowed, with minimal experimentation and by multiple regression, to deduce an equation, which correlates the logarithm of the first order kinetic constant (log k') with reaction temperature, DMF concentration, and hydrophobicity (log P values) of the different protecting groups. The predictive value of the equation was tested by comparing the performance of another protective group, such as Aloc, with the performance predicted by said equation. Experimental and calculated k' values were found to be in good agreement.