Dual shape recovery of red blood cells flowing out of a microfluidic constriction

International audienceMicropipette aspiration, optical tweezers, rheometry, or ecktacytometry have been used to study the shape recovery of healthy human Red Blood Cells (RBCs) and measure associated relaxation times of the order of 100–300 ms. These measurements are in good agreement with the Kelvin–Voigt model, which describes the cell as a visco-elastic material, predicting that its relaxation time only depends on cell intrinsic properties. However, such mechanical solicitation techniques are far from being relevant regarding RBC solicitation in vivo. In this paper, we report for the first time the existence of two different behaviors of the RBC shape recovery while flowing out of a microfluidic constricted channel. The calculation of the viscous stress corresponding to the frontier between the two recovery modes confirms that the RBC resistance to shear μ is the elastic property dominating the transition between the two recovery behaviors. We also quantified associated recovery times τr and report values as low as 4 ms—which is almost two decades smaller than the typical RBC relaxation time—at high viscosity and flow velocity of the carrier fluid. Although we cannot talk about relaxation time because the cell is never at rest, we believe that the measured shape recovery time arises from the coupling of the cell intrinsic deformability and the hydrodynamic stress. Depending on the flow conditions, the cell mechanics becomes dominant and drives the shape recovery process, allowing the measurement of recovery times of the same order of magnitude than relaxation times previously published. Finally, we demonstrated that the measurement of the shape recovery time can be used to distinguish Plasmodium falciparum (causing malaria) infected RBCs from healthy RBCs

7-Chloro-4-aminoquinoline γ-hydroxy-γ-lactam derived-tetramates as a new family of antimalarial compounds

International audienceIn this Letter we report on an efficient and short 2–3 steps synthesis of γ-hydroxy-γ-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline skeleton and their evaluation as potent antimalarials. These molecules were obtained through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived amines. In vitro antimalarial activity of these new γ-lactams was evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and they were found to be active in the range of 14–827 nM with generally good resistance index. A preliminary SAR study is also presented to explain these results. Finally, the most active compounds did not show in vitro cytotoxicity when tested against Human Umbilical Vein Endothelial Cells (HUVEC) up to concentration of 50 μM and they were stable at pH 7.4 for at least 48 h

Hétérocycles azotés dérivés d'acides tétramiques et de pyrimidines comme nouveaux agents anti-infectieux : activité antipaludique et anti-pneumocystose

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Hétérocycles azotés dérivés d'acides tétramiques et de pyrimidines comme nouveaux agents anti-infectieux : activité antipaludique et anti-pneumocystose

National audienc

g-Hydroxy- g- lactam derivated tetramates as a new family of antimalarials

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g-Hydroxy- g- lactam derivated tetramates as a new family of antimalarials

National audienc

Nouveaux dérivés antipaludiques dérivés de acides gamma-hydroxy tétramiques

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Nouveaux dérivés antipaludiques dérivés de acides gamma-hydroxy tétramiques

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Interaction between environment, nutrient-derived metabolites and immunity: A possible role in malaria susceptibility/resistance in Fulani and Dogon of Mali

<div><p>The role of some nutrient-derived metabolites on the innate and adaptive immune responses is now established. Global research approach investigating the interplay between environment, lifestyle and the host’s immune responses is crucial in the understanding of malaria susceptibility. Advanced Glycation end products (AGE), which are food-derived metabolites result from the link between reducing sugar and amino group of proteins, lipids or nucleic acids. The level of exposure to AGEs varies depending on the type of diet. The dysfunction of the immune system induced by AGE and the cellular receptors for AGEs (RAGE) in susceptibility to bacterial infection has been described. But no study has yet explored their role in susceptibility to malaria. Therefore, we aimed to evaluate systemic AGE and RAGE gene polymorphism in two sympatric populations with previously described difference of susceptibility to malaria. We measured by ELISA the plasma levels of AGEs, and their soluble receptors (sRAGE) from 170 volunteers (68 Fulani and 102 Dogon). We also determined by real-time quantitative PCR the expression of RAGE, and the -374 T/A, -429 T/C polymorphisms and 63 bp deletion by fragment length restriction polymorphism. The prevalence rate of <i>Plasmodium</i> in Fulani and Dogon were respectively 42.64% and 51.30% for <i>P</i>. <i>falciparum</i>, 5.88% and 6.5% for <i>P</i>. <i>malariae</i>, 0% and 2.6% for <i>P</i>. <i>ovale</i>. The average AGE was 12.65 μg/ml, and 496.48pg/ml for sRAGE. Highest levels of sRAGE were observed in Fulani (563,07pg/ml, 95% CI [547.81–580.13] vs 465.68pg/ml, 95% CI [331.19–467.51]) for Dogon, p = 0.00001. Fulani had the lowest mean of AGE (10.21μg/ml, 95% CI [8.02–10.92]) compared to Dogon (16.88μg/ml, 95% CI [13.92–17.96]; p = 0.00001. RAGE was more expressed in Dogon than Fulani (0.08 vs 0.04), P = 0.08. The -374A polymorphism vas more frequent in Fulani (32%) compared to Dogon (20%). The chronic exposure to dietary AGE could lead to immune responses impairment and polymorphism with implications in malaria susceptibility. More studies are necessary to better investigate this hypothesis.</p></div

Distribution of the mean of sRAGE by age groups in Fulani and Dogon.

<p>Distribution of the mean of sRAGE by age groups in Fulani and Dogon.</p