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The bioaccumulation of mercury by fish was studied in three natural lakes lining the Tapajós River, Brazilian Amazon. The Hg content variations are also reported between the rainy and the rising water seasons. Position of fish in the food chain and the source of carbon at the base of the food chain were determined using nitrogen and carbon stable isotopes ratios respectively. During the two seasons, the effect of the Hg biomagnification between the non-piscivorous and piscivorous fish of the three lakes is observed. The correlation between the mercury concentrations and the nitrogen isotopic ratios suggests that the fish mercury content variability is connected with the trophic position and size. Aside from classic observations on mercury biomagnification by certain species of fish (i.e. contents increase with size or trophic status), novel results were revealed as well, such as some species decrease of mercury contents with size of fish. Aquatic organisms in the Amazon are adapted to the complexity of trophic webs coupled with changes in environmental variables, depending on the location and/or the season, which results in a wide range of mercurial contamination among the Tapajós ichthyofauna. [ABSTRACT FROM AUTHOR]

Excessive lipid intake, associated with a qualitative imbalance, favors the development of obesity and associated diseases. From organs involved in the lipid homeostasis, the small intestine remains the most poorly known although it is responsible for the lipid bioavailability and largely contributes to the regulation of postprandial hypertriglyceridemia. The mechanism of long chain fatty acid (LCFA) intestinal absorption is not totally elucidated. Over the two last decades, cloning of lipid binding proteins (LBP), proteins involved in trafficking and metabolic fate of LCFA in gut have provided new insights on cellular and molecular mechanisms involved in fat absorption. The synthesis of recent literature indicates that intestine is able to adapt its absorption capacity to the fat content of the diet. This adaptation takes place through a fat-coordinated induction of LBP and apolipoproteins. CD36 could operate as a lipid sensor responsible for a transducing signal related to the lipid content of the diet at the origin of this intestinal adaptation. This lipid-mediated metabolic response may lead to the formation of large chylomicrons rapidly degraded in the blood. All together, these new data indicate that this intestinal lipid sensing mechanism may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks.

Conjugated linoleic acid (CLA) refers to a class of positional and geometric dienoic isomers of linoleic acid. Chronic dietary supplementation with a commercial mixture containing c9,t11-CLA and t10,c12-CLA in equimolar quantity leads to a drop in fat mass in various species. The t10,c12-CLA isomer is responsible for this anti-obesity effect. The reduction of fat mass is especially dramatic in the mouse, in which it is associated with a severe hyperinsulinemia, an insulin resistance and a massive liver steatosis. The origin of these adverse side effects and the putative chronology of events leading to CLA-mediated lipoatrophic syndrome are presented and discussed in this review.

Purpose of the study. – To underline value of the preoperative splenic embolization with haemostatic aim to facilitate partial splenectomy.Material. – Observation of a 23-year-old woman, admitted for pain, anemia, and mass of the left hypochondrium. Sonography, helical CT and MRI showed that the bulky mass was developed from the upper pole of spleen, and dislodged the left kidney towards the pelvis. This mass had fibrous characteristics in favour of a primary lesion with recent bleeding and was compatible with a splenic hamartoma.Methods. – Selective partial splenic embolization with haemostatic aim using metal coils, immediately followed by surgery.Results. – Preoperative embolisation made possible to carry out under optimal surgical conditions a partial splenectomy with en-bloc resection of the splenic mass. Histologic diagnosis was splenic hamartoma of pulpar type.Conclusion. – This case illustrates the interest of accurate characterization of splenic lesions by several imaging techniques allowing indication for conservative surgery, and of preoperative embolization facilitating a partial splenectomy. [Copyright &y& Elsevier]

DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a selective inhibitor of human Polθ (encoded by POLQ). A high-throughput screening campaign of 350,000 compounds identified an 11 micromolar hit, giving rise to the N2-substituted fused pyrazolo series, which was validated by biophysical methods. Structure-based drug design efforts along with optimization of cellular potency and ADME ultimately led to the identification of RP-6685 : a potent, selective, and orally bioavailable Polθ inhibitor that showed in vivo efficacy in an HCT116 BRCA2 -/- mouse tumor xenograft model.