The 24h urinary cortisol/cortisone ratio and epinephrine/norepinephrine ration for monitoring training in young female tennis players

International audienc

Effects of VEGF blockade on the dynamics of the inflammatory landscape in glioblastoma-bearing mice

International audienc

On-ticagrelor platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome

International audienceBackground: A strong association between on-thienopyridines platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting.Objectives: We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI.Methods: We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction and urgent revascularization.Results: We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥ 2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥ 2 or with MACE (p=0.12 and p=0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor qualitatively (low on-treatment PR (LTPR) vs no LTPR).Conclusion: On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor

Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome

International audienceBACKGROUND:Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome.OBJECTIVES:We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI).METHODS:We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR.RESULTS:Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis.CONCLUSION:In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis

Respiration was similar in brain mitochondrial preparations from 24-month-old <i>PARK2^−/−</i> and wild type mice examined with standard oxygraphy.

<p>(<b>A</b>) Representative experiment with a crude mitochondrial pellet from striatum. Blue curve = oxygen (O₂) concentration expressed as nmol/mL; red curve = rate of oxygen consumption expressed as nmoles O₂/mL and min; ADP = addition of 400 µM ADP; OM = addition of 1 µg/mL oligomycin, a complex V inhibitor; KCN = addition of 1 mM KCN (non-respiratory oxygen consumption); (<b>B, C, D</b>) Bars showing state 3 respiration (respiration in the presence of substrates +ADP – non-respiratory oxygen consumption) and state 4 respiration (respiration in the presence of oligomycin – non-respiratory oxygen consumption) on complex I substrates (glutamate+malate); black bars = <i>PARK2^−/−</i>, white bars = wild type; data are expressed as nmoles O₂/mL and mg proteins and are shown as means ± SD; two animals, one per genotype, were analyzed the same day; the numbers between brackets indicate the number of individual animals of each genotype; (B) results from crude mitochondrial pellets from striatum (n = 6), (C) crude mitochondrial pellets from cortex (n = 7) and (D) purified mitochondria from whole brain (n = 2).</p

Increase of the mitochondrial glutathione content in striatum of 12-month-old <i>PARK2</i>^−/− mice.

<p>Total glutathione (GSH+GS-SG) levels were determined in cytosols and isolated mitochondria from ventral midbrain and striatum of 12- and 24-month-old <i>PARK2^−/−</i> (black bars) and wild-type mice (white bars), data are expressed as mean and SD of five independent measurements for each age and each genotype. * = p<0.05 using multiple comparison with Holm-Sidak test. Significant differences with age, without influence of the genotype, were observed for midbrain mitochondrial and striatal cytosolic glutathione content. Significant interaction between age and genotype was present for striatal mitochondrial glutathione content, which significantly increased with age only in wild type mice and was at 12 months of age significantly higher in <i>PARK2^−/−</i> than in wild type mice.</p

Proteasome activities were similar in <i>PARK2^−/−</i> and wild type mice.

<p>Chymotrypsin-like activity of the proteasome. Results are expressed as nmoles of substrate cleaved/minute and milligram of protein and as mean±standard deviation of n = 5 measurements.</p

Presence of oxidative adducts in striatal crude mitochondrial pellets from <i>PARK2</i>^−/− mice.

<p>Western blot analysis of proteins from crude mitochondrial pellets from striatum (A) and midbrain (B) of <i>PARK2</i>^−/− and wild-type mice, at 12 and 24 months of age; loading control was the outer membrane protein Voltage-Dependent Anion Channel (VDAC); (C) densitometric analysis of oxidative adducts was performed in the length of the membrane shown in A and B, that signal was then normalized to VDAC signal and quantification was expressed as means and SD and as % of the mean of wild-type samples on the membrane shown in A and B; * = p<0.05 using Mann and Whitney test.</p

Maximal respiration is reduced in striatal neurons from <i>PARK2^−/−</i> mice.

<p>Representative experiments with neurons or astrocytes from striatum or cortex: the traces represent the evolution of the respiration rate (in pmol O₂/minute) in Seahorse plates seeded with cells from <i>PARK2^−/−</i> (black circles) and wild type (white circles) mice. Sequential additions are: oligomycin (OM) (0.25 µg/ml for neurons and 0.5 µg/ml for astrocytes), fccp (FP) (3 µM for cortical neurons and 1 µM for other cells), and rotenone+antimycine (RA) (50 nM rotenone+150 µg/ml antimycin A). Bars below the traces show the means and SD of basal respiration, maximal respiration and spare respiratory capacity (SRC = maximal – basal respiration) of 3 independent tests, each performed in 6 to 12 independent wells. * <i>p</i><0.05 using Mann and Whitney test.</p

The inner mitochondrial membrane potential is normal in midbrain and striatum of <i>PARK2</i>^−/− mice.

<p>Dark circles = <i>PARK2^−/−</i>, white circles = wild type; ΔΨm = inner mitochondrial membrane potential expressed as mV after transformation of the fluorescent rhodamine 123 signal using the Nernst equation, as explained in the methods section; A = ΔΨm in the presence of glutamate+malate; B = A+1 mM ADP; C = B+1 µM oligomycin; D = C+1 µM cccp; E = C+2 µM cccp; F = C+4 µM cccp;G = C+8 µM cccp. The data were obtained in parallel to the analysis of respiration; two animals, one per genotype, were analyzed the same day; the data obtained from seven 9-month-old mice and six 24-month-old ones of each genotype, they are expressed as mean and SD.</p