In this study, the multivariate partial least-squares projections to latent structures (PLS) technique was used for modeling the brain-blood concentration ratio (BB) of 61 structurally diverse compounds. The PLS model was based on molecular descriptors that can be calculated for any compound simply from a knowledge of its molecular structure, and the model included several topological and constitutional descriptors. The PLS analysis resulted in a significant three-component model with the following statistics: r = 0.922, Q = 0.867, s = 0.318, n = 58, and F = 102. The predictive ability of the model was assessed by means of crossvalidation and also by using BB partitioning data, BBB permeability data, and 1 set of qualitative brain penetration data, resulting in BB distribution data for 97 compounds. The results indicate that the PLS model developed is statistically sound and is sufficiently robust for predictive use. Taking into account the great ease of computation and interpretation of the derived model, it may be of general utility in predicting BB ratios for a very wide range of new drugs.

Quantitative structure-activity relationships have been developed for a set of 107 inhibitors of the HIV-1 reverse transcriptase, derivatives of a recently reported HIV-1 specific lead: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The activity of these compounds was investigated by means of multiple linear regression (MLR) and PLS regression techniques and topological indexes as well as several tabulated physicochemical substituent constants were used as predictor variables. The results obtained indicate that the anti-HIV activity of the HEPT derivatives is strongly dependent on hydrophobic factors as expressed by the Hansch constant (sigma pi (R1+R2)), and especially dependent on the geometric factors mainly accounted for by the 1 chi N (R2) and 4 chi pN molecular connectivity indexes and also for the molecular volume (Vx), the Taft steric constant (Es(2R1)), and the Verloop parameter for the smallest width value (B1(3R1)). Besides, for this data set, comparison of the quality of MLR and PLS models show that PLS is a better approach to MLR for improving the interpretability of the data and also to exhibit models with a better predictive quality.

Plants constitute an alternative source of proteins in the human diet, with advantages over animal proteins because of their low content of saturated fats and absence of cholesterol. Within the framework of a wider research project on the role of Amaranthus cruentus (Ac) in lipid metabolism, in this work the chemical composition and biological value of the Ac flour and its protein concentrate were compared. Proximate chemical composition, amino acid and fatty acid profiles, some antinutrient factors, and biological values were determined for Ac seed flour and its protein concentrate obtained by extraction at pH 11 and precipitation at pH 4.5. The flour protein content was 16.6 g% while that of the concentrate was 52.56 g%. The content of the soluble dietary fiber with a hypolipemic function was notably higher in the protein concentrate (12.90 g%) than in the seed flour (4.29 g%). The protein concentrate also exhibited a higher content of insoluble dietary fiber. The Ac flour and the concentrate contain 75.44 and 56.95% unsaturated fatty acids, respectively. Squalene, which affects the biosynthesis of cholesterol, was detected both in the flour and the concentrate oils, with a higher content in the concentrate (9.53%) as compared to the flour (6.23%). Comparison of the amino acid composition with the FAO pattern protein indicated that the concentrate does not have limiting amino acids, while the flour has leucine, threonine, and valine. The content of lysine was high in both the flour and the concentrate, making these products particularly useful as a complement for cereal flour, which is deficient in this amino acid. The biological quality analysis demonstrated an improvement in the quality of the concentrate. The presence of saponins, phytic acid, and trypsin inhibitors in the concentrate, which favor the metabolism of lipids, suggests that consumption of the concentrate might reduce the risk of heart disease.

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The present study was undertaken to assess whether chronic exposition to cadmium (Cd, 0.133 mM per liter for 2 months) through drinking water may affect the lipid contents in the pituitary anterior lobe (PAL) of adult male Wistar rats. As compared to metal non-exposed controls, PALs exposed to cadmium showed an increase in total phospholipid contents, which was associated to an increase of the incorporation of [1-14C]-methyl choline into phosphatidylcholine and of [U-14C]-glucose into total phospholipids. The incorporation of [1-14C]-methyl choline into sphingomyelin was not changed. Incorporation of [1-14C]-acetate into total fatty acids also increased but incorporation of [1-14C]-acetate into cholesterol did not change. The activity of phospholipase D decreased both in PALs from Cd exposed rats and in PAL dispersed cells treated with Cd in the culture medium from Cd non-exposed rats. In PALS from Cd exposed rats, a decrease of serum prolactin and growth hormone concentrations was determined. The results shown that cadmium modifies the lipid contents of pituitary gland and directly or indirectly the levels of prolactin and growth hormone in serum.