Background-Steady laminar flow is atheroprotective, in part because of its antiinflammatory effects on vascular endothelial cells (ECs). We studied the activation of peroxisome proliferator-activated receptor-␥ (PPAR␥) in ECs in response to laminar flow and the associated antiinflammatory effect. Methods and Results-Using flow channel with cultured ECs, we found that laminar flow activated the PPAR␥-mediated PPAR-responsive element (PPRE) activity and increased the mRNA encoding CD36, a PPAR␥-targeted gene. Analysis of the CD36 promoter revealed that PPRE was required for flow activation. Laminar flow induced the GAL-PPAR␥-LBD fusion protein, which suggests that flow activation of PPAR␥ was ligand dependent. The pharmaceutical inhibitors of phospholipase A2 (PLA2) and cytochrome P450 epoxygenases (CYP450s) were able to block the laminar flow-activated PPAR␥. We also showed that lipid extracts from flow media contained ligands for the activation of PPAR␥ in other cell types. This paracrine activation exerted antiinflammatory effects in ECs and THP-1 cells, including the suppression of cytokine-induced nuclear factor-B activation and expression of intercellular adhesion molecule-1. Key Words: cells, endothelial Ⅲ receptors, peroxisome proliferator-activated Ⅲ inflammation D epending on the geometry of the arterial tree, blood flow in the straight part of vessels is steady and laminar, whereas that in the bends and branches is disturbed. 1 The focal distribution of atherosclerotic lesions in the disturbed flow areas indicates the pivotal role of local flow in atherogenesis. 2 Because early atherosclerotic events involve the inflammatory responses of vascular endothelial cells (ECs), disturbed flow patterns with high shear stress gradients are considered to be proinflammatory, whereas steady laminar flow is antiinflammatory. 3,4 Using flow channel systems, we and others demonstrated that the application of flow to cultured ECs transiently induced genes encoding chemoattractants, adhesion molecules, and cytokines, which is due in part to the activation of nuclear factor-B (NF-B) and AP-1. 5,6 The induction of these genes has been suggested to be the endothelial response to the rapid change of shear stress (/t). 7 In agreement with this hypothesis, prolonged laminar flow suppresses the expression of proinflammatory molecules. 8 To date, the molecular basis underlying the antiinflammatory effect of laminar flow is still elusive. Conclusions-LaminarPeroxisome proliferator-activated receptor (PPAR) -␣, -␤/␦, and -␥ constitute a subfamily of nuclear receptors. Among PPARs, PPAR␥ is largely expressed in monocytes/ macrophages, adipocytes, and intestinal cells in which PPAR␥ regulates genes involved in cell differentiation and lipid uptake and storage (eg, aP2, CD36). 9 The ligand-binding domain (LBD) of PPAR␥ can bind a wide range of ligands that have distinct structures, 10 including the natural ligand 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) and synthetic ligand thiozolidinediones (TZDs). PPAR␥ is also present in...

Objective: To develop guidelines for low back pain management according to previous international guidelines and the updated literature.Methods: A report was compiled from a review of systematic reviews of guidelines published between 2013 and 2018 and meta-analysis of the management of low back pain published between 2015 and 2018. This report summarized the state-of-the-art scientific knowledge for each predefined area of the guidelines from a critical review of selected literature. A multidisciplinary panel of experts including 17 health professionals involved in low back pain management and 2 patient representatives formulated preliminary guidelines based on the compilation report and a care pathway. The compilation report and preliminary guidelines were submitted to 25 academic institutions and stakeholders for the consultation phase. From responses of academic institutions and stakeholders, the final guidelines were developed. For each area of the guidelines, agreement between experts was assessed by the RAND/UCLA method. Results:The expert panel drafted 32 preliminary recommendations including a care pathway, which was amended after academic institution and stakeholder consultation. The consensus of the multidisciplinary expert panel was assessed for each final guideline: 32 recommendations were assessed as appropriate; none was assessed as uncertain or inappropriate. Strong approval was obtained for 27 recommendations and weak for 5. Conclusion:These new guidelines introduce several concepts, including the need to early identify low back pain at risk of chronicity to provide quicker intensive and multidisciplinary management if necessary.

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The purpose of this study was to compare the adrenal medullar responsiveness to the sympathetic nervous activity between sprinters and untrained subjects after a supramaximal exercise (Wingate-test). Thirteen subjects took part in this study: 7 male athletes (20.3+/-1.8 years) competing in sprint running (S) and 6 untrained men (UT) (21+/-1.3 years). They performed an incremental treadmill test to determine the maximal oxygen uptake (VO2max), a force-velocity test and a Wingate-test on 3 different days, separated by a maximal interval of 15 days. The maximal power (Wmax) and the mean power (W) were determined from the Wingate-test on a cycle ergometer. Plasma lactate, adrenaline and noradrenaline concentrations were determined at rest (La0, A0, NA0), immediately after the Wingate-test (Amax, NAmax) and after 5 minutes recovery (Lamax, A5 and NA5). S exhibited higher performances than UT during the Wingate-test as shown by their significantly higher values of Wmax (1111+/-38 w in S vs 886+/-148 w in UT), W (822+/-37 w in S vs 646+/-69 w in UT) and Lamax (16.8+/1.8 mmol x l(-1) in S vs 12.2+/-2.5 mmol x l(-1) in UT). At the end of the test the NAmax values were similar in both groups whereas the Amax were significantly higher in S (7.6 +/- 1.4 nmol x l(-1) in S vs 3.6 +/- 3.2 nmol x l(-1) in UT). This leads to a higher Amax/NAmax ratio for sprinters compared to untrained subjects (0.7+/-0.2 in S vs 0.3+/-0.2 in UT, p < 0.05). As the disappearance of A (estimated by the Amax-A5 difference) was not lower in S (6.4+/1.5 nmol x l(-1) in S vs 1.8+/-4 nmol x l(-1) in UT), the higher Amax values in S might be explained by a greater secretion level of A. Conversely the identical NAmax values in both groups suggested that this kind of exercise induced the same sympathetic input in S and UT. Consequently the higher Amax/NAmax ratio in S argued in favor of a higher responsiveness of the adrenal medulla of sprinters to the same sympathetic input.