Problèmes médico-légaux posés par un préjudice sexuel déclaré après un dommage corporel

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Temporal schemes of PUFA-producing enzymes and metabolites upon ischemia-reperfusion.

<p><b>A</b>, Kinetic scheme of COX, LOX and CYP activation based on PUFA metabolites enzymatic biosynthesis. Early ischemia induces LOX metabolite biosynthesis, while COX activation seems to play a major role during the first hours after reperfusion (2 and 5 hours). CYP-derived metabolite synthesis starts immediately during ischemia and up to 5 hours reperfusion. <b>B,</b> Scheme of temporal PUFA metabolites production during intestinal ischemia reperfusion injury. Ischemic episodes (induction of the inflammatory response) lead to a concomitant early production of both the neutrophil chemo-attractant LTB₄ and the vascular-protective LxA₄. Immediate biosynthesis of LxA₄ could assure an appropriate counterbalance role against ischemic damage. From 2 hours and up to 5-h reperfusion, PGE₂ (such as other COX-derived metabolites) production was strongly increased fitting with the concomitant peaks of mucosal damage (2 hours) and granulocyte recruitment (5 hours). LTB₄ (such as other LOX-derived metabolites) again significantly increased after 5 h of reperfusion, suggesting that at this time-point, additional cell source (potentially granulocytes) is responsible for the biosynthesis of LOX metabolites. At 24-h after reperfusion, all PUFA metabolites were decreased, to reach basal levels after 48 h of reperfusion, except for mediators known to take part into the resolution of inflammation: the RvE precursor 18-HEPE and the PPARγ agonist, 15d-PGJ₂.</p

Effect of ischemia on intestinal CYP-derived eicosanoids production.

<p>Synthesis of eicosanoids from arachidonic acid (AA) was measured by liquid chromatography-tandem mass spectrometry in control mice (naïve and sham operated mice) and following 50 minutes of ischemia. Data represent means ± SEM of 6 to 8 mice per group. *p<0.05, and ***p<0.001 <i>versus</i> the corresponding sham operated group.</p

Effect of ischemia followed by reperfusion from 2 to 48 hours on intestinal eicosanoids/docosanoid production.

<p><b>A</b>–<b>D</b> Synthesis of eicosanoids derived from COX-(<b>A</b>) LOX-(<b>B</b>) CYP-(<b>C</b>) arachidonic acid (AA) or its precursor the dihomo-γ-linolenic acid (DGLA) metabolism. <b>D,</b> Synthesis of docosanoid derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) metabolism. Data are expressed as fold increase <i>versus</i> corresponding sham operated group and represent means ± SEM of 6 to 8 mice per group.</p

Effect of ischemia on intestinal docosanoid metabolites production.

<p>Synthesis of docosanoids from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was measured by liquid chromatography-tandem mass spectrometry in control mice (naïve and sham operated mice) and following 50 minutes of ischemia. Data represent means ± SEM of 6 to 8 mice per group. *p<0.05, and **p<0.01 <i>versus</i> the corresponding sham operated group.</p

<i>In vivo</i> effects of systemic treatment with the transient receptor potential vanilloid-4 antagonist HC-067047 (50 mg/kg i.p.) or its vehicle.

<p>A, histological damage; B, microscopic damage (white) and MPO activity (grey); C–E chemokine (KC, MCP-1 and IL-6) tissue protein expression. Data in B, C, D and E represent means ± SEM of 6 to 8 mice per group. *p<0.05, **p<0.01, ***p<0.001 <i>versus</i> the corresponding sham operated group +p<0.05 <i>versus</i> the indicated I–R group.</p

Quantification and Potential Functions of Endogenous Agonists of Transient Receptor Potential Channels in Patients With Irritable Bowel Syndrome

In mice, activation of the transient receptor potential cation channels (TRP) TRPV1, TRPV4, and TRPA1 causes visceral hypersensitivity. These receptors and their agonists might be involved in development of irritable bowel syndrome (IBS). We investigated whether polyunsaturated fatty acid (PUFA) metabolites, which activate TRPs, are present in colon tissues from patients with IBS and act as endogenous agonists to induce hypersensitivity

Altered Subpopulations of Red Blood Cells and Post-treatment Anemia in Malaria

International audienceIn acute malaria, the bulk of erythrocyte loss occurs after therapy, with a nadir of hemoglobin generally observed 3–7 days after treatment. The fine mechanisms leading to this early post-treatment anemia are still elusive. We explored pathological changes in RBC subpopulations by quantifying biochemical and mechanical alterations during severe malaria treated with artemisinin derivatives, a drug family that induce “pitting” in the spleen. In this study, the hemoglobin concentration dropped by 1.93 G/dl during therapy. During the same period, iRBC accounting for 6.12% of all RBC before therapy (BT) were replaced by pitted-RBC, accounting for 5.33% of RBC after therapy (AT). RBC loss was thus of 15.9%, of which only a minor part was due to the loss of iRBC or pitted-RBC. When comparing RBC BT and AT to normal controls, lipidomics revealed an increase in the cholesterol/phosphatidylethanolamine ratio (0.17 versus 0.24, p &lt; 0.001) and cholesterol/phosphatidylinositol ratio (0.36 versus 0.67, p = 0.001). Using ektacytometry, we observed a reduced deformability of circulating RBC, similar BT and AT, compared to health control donors. The mean Elongation Index at 1.69Pa was 0.24 BT and 0.23 AT vs. 0.28 in controls ( p &lt; 0.0001). At 30Pa EI was 0.56 BT and 0.56 AT vs. 0.60 in controls ( p &lt; 0.001). The retention rate (rr) of RBC subpopulations in spleen-mimetic microsphere layers was higher for iRBC (rr = 20% p = 0.0033) and pitted-RBC (rr = 19%, p = 0.0031) than for healthy RBC (0.12%). Somewhat surprisingly, the post-treatment anemia in malaria results from the elimination of RBC that were never infected

PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells

<div><p>Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor critical in the developing brain. We observed that HCMV infection dramatically impaired the rate of neuronogenesis and strongly increased PPARγ levels and activity. Consistent with these findings, levels of 9-hydroxyoctadecadienoic acid (9-HODE), a known PPARγ agonist, were significantly increased in infected NSCs. Likewise, exposure of uninfected NSCs to 9-HODE recapitulated the effect of infection on PPARγ activity. It also increased the rate of cells expressing the IE antigen in HCMV-infected NSCs. Further, we demonstrated that (1) pharmacological activation of ectopically expressed PPARγ was sufficient to induce impaired neuronogenesis of uninfected NSCs, (2) treatment of uninfected NSCs with 9-HODE impaired NSC differentiation and (3) treatment of HCMV-infected NSCs with the PPARγ inhibitor T0070907 restored a normal rate of differentiation. The role of PPARγ in the disease phenotype was strongly supported by the immunodetection of nuclear PPARγ in brain germinative zones of congenitally infected fetuses (N = 20), but not in control samples. Altogether, our findings reveal a key role for PPARγ in neurogenesis and in the pathophysiology of HCMV congenital infection. They also pave the way to the identification of PPARγ gene targets in the infected brain.</p></div