[Palm oil derivatives with different concentration of palmitic acid and antioxidants. Effects upon plasmatic lipids and platelet aggregation]. / Derivados del aceite de palma con concentraciones diferentes de ácido palmítico y antioxidantes. Efectos sobre lípidos plasmáticos y agregación plaquetaria.

It was evaluated the effect of diet rich with cholesterol (0.1%) and different concentration of palmitic acid (16:0) and antioxidants (vitamin C, alpha tocopherol and retinol) upon plasmatic lipids and platelet aggregability in rabbits. The animals were distributed in three groups: I. Standard chow meal (Rp Conejarina) + cholesterol (chol) 0.1%; II. Standard chow meal + chol 0.1% + semipurified palm oil 10% (16:0 = 39.8%, oleic acid 48.7%, linoleic acid 11.4%, retinol 7.3 ug/dL, alpha tocopherol 157.6 ug/dL; III. Standard chow meal + chol 0.1% + crude palm oil 10% (16:0 = 45.3%, oleic acid 46.3%, linoleic acid 7.9%, retinol 96.4 ug/dL, alpha tocopherol 322.8 ug/dL). Monthly determination of plasmatic lipids were done (Enzymatic methods) and at ten months platelet aggregability with ADP, plasmatic vitamin C, retinol and, alpha tocopherol determination were done. Total plasmatic cholesterol (TC) and LDLc increased significantly in the three groups of animals. Significant differences between groups were not found. Platelet aggregability was lower in the animals fed with palmitic acid rich diet (groups II and III) (P = 0.002 and 0.001). Retinol, alpha tocopherol plasmatic concentrations revealed no significant differences. Vitamin C in the groups I was lower than groups II and III (P < 0.05 < 0.02). In this study hypercholesterolemic rabbits fed with rich diets (crude and semipurified) had lower platelet aggregability without changes in plasmatic lipids concentrations.

[Effects of cholestasis on hepatotoxicity of acetaminophen in rats]. / Efectos de la colestasis sobre la toxicidad hepatica del acetaminofen en ratas.

Acetaminophen high doses toxicity has been reported in clinical and experimental studies in relation with cytochrome P-450. (Acetaminophen metabolite). Thinking that biliary tract obstructions hould increases drugs toxicity because interferes toxic substances excretion or it modify the activity of P-450 we decided to study acetaminophen toxicity in rats with biliary tract obstruction. Male sprague Dawley rats were used (body weight 250-400 gr) in two groups: Group I control (6 rats) with choledoco bile duct ligated; two doses of saline solution 0.9% Intraperitoneal, 0.2 ml/100 gr. were administrated. Group II (Same surgical intervention) received two doses of acetaminophen (intraperitoneal) solution (400 mg/Kg). This group was divided in two (6 rats each), one of this was sacrificed at 48 h. and the other one at 120 h. after acetaminophen injection. Total, direct and indirect bilirubin, alkaline phosphatase, ALT and AST transaminases, hematology study, liver weight, histological studies of liver and kidney were performed in all rats. High incidence of liver necrosis ans significative transaminases increases were found in group II. Our results were discussed taking account that recent biliary tract obstruction increase acetaminophen toxicity, at a half doses reported in other studies. It is possible that mixed oxidation system activity of cytochrome P-450 was increased in our research.

Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine.

In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma-globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.