Anti-Inflammatory Effect of Fluvastatin on IL-8 Production Induced by Pseudomonas aeruginosa and Aspergillus fumigatus Antigens in Cystic Fibrosis

International audienceBACKGROUND: Early in life, patients with cystic fibrosis (CF) are infected with microorganisms including bacteria and fungi, particularly Pseudomonas aeruginosa and Aspergillus fumigatus. Since recent research has identified the anti-inflammatory properties of statins (besides their lipid-lowering effects), we investigated the effect of fluvastatin on the production of the potent neutrophil chemoattractant chemokine, IL-8, in whole blood from CF patients, stimulated by Pseudomonas aeruginosa (LPS) and Aspergillus fumigatus (AFA) antigens. RESULTS: Whole blood from adult patients with CF and from healthy volunteers was collected at the Rennes University Hospital (France). Blood was pretreated for 1 h with fluvastatin (0-300 µM) and incubated for 24 h with LPS (10 µg/mL) and/or AFA (diluted 1/200). IL-8 protein levels, quantified by ELISA, were increased in a concentration-dependent manner when cells were stimulated by LPS or AFA. Fluvastatin strongly decreased the levels of IL-8, in a concentration-dependent manner, in whole blood from CF patients. However, its inhibitory effect was decreased or absent in whole blood from healthy subjects. Furthermore, the inhibition induced by fluvastatin in CF whole blood was reversed in the presence of intermediates within the cholesterol biosynthesis pathway, mevalonate, farnesyl pyprophosphate or geranylgeranyl pyrophosphate that activate small GTPases by isoprenylation. CONCLUSIONS: For the first time, the inhibitory effects of fluvastatin on CF systemic inflammation may reveal the important therapeutic potential of statins in pathological conditions associated with the over-production of pro-inflammatory cytokines and chemokines as observed during the manifestation of CF. The anti-inflammatory effect could be related to the modulation of the prenylation of signalling proteins

Operating a full tungsten actively cooled tokamak: overview of WEST first phase of operation

WEST is an MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: (i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; (ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017–2020), a set of actively cooled ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW m−2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about 1 min achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also described

WEST full tungsten operation with an ITER grade divertor

The mission of WEST (tungsten-W Environment in Steady-state Tokamak) is to explore long pulse operation in a full tungsten (W) environment for preparing next-step fusion devices (ITER and DEMO) with a focus on testing the ITER actively cooled W divertor in tokamak conditions. Following the successful completion of phase 1 (2016-2021), phase 2 started in December 2022 with the lower divertor made entirely of actively cooled ITER-grade tungsten mono-blocks. A boronization prior the first plasma attempt allowed for a smooth startup with the new divertor. Despite the reduced operating window due to tungsten, rapid progress has been made in long pulse operation, resulting in discharges with a pulse length of 100 s and an injected energy of around 300 MJ per discharge. Plasma startup studies were carried out with equatorial boron nitride limiters to compare them with tungsten limiters, while Ion Cyclotron Resonance Heating assisted startup was attempted. High fluence operation in attached regime, which was the main thrust of the first campaigns, already showed the progressive build up of deposits and appearance of dust, impacting the plasma operation as the plasma fluence increased. In total, the cumulated injected energy during the first campaigns reached 43 GJ and the cumulated plasma time exceeded 5 h. Demonstration of controlled X-Point Radiator regime is also reported, opening a promising route for investigating plasma exhaust and plasma-wall interaction issues in more detached regime. This paper summarises the lessons learned from the manufacturing and the first operation of the ITER-grade divertor, describing the progress achieved in optimising operation in a full W environment with a focus on long pulse operation and plasma wall interaction

Inter-machine comparison of intrinsic toroidal rotation in tokamaks

Parametric scalings of the intrinsic (spontaneous, with no external momentum input) toroidal rotation observed on a large number of tokamaks have been combined with an eye towards revealing the underlying mechanism(s) and extrapolation to future devices. The intrinsic rotation velocity has been found to increase with plasma stored energy or pressure in JET, Alcator C-Mod, Tore Supra, DIII-D, JT-60U and TCV, and to decrease with increasing plasma current in some of these cases. Use of dimensionless parameters has led to a roughly unified scaling with M-A alpha beta(N), although a variety of Mach numbers works fairly well; scalings of the intrinsic rotation velocity with normalized gyro-radius or collisionality show no correlation. Whether this suggests the predominant role of MHD phenomena such as ballooning transport over turbulent processes in driving the rotation remains an open question. For an ITER discharge with beta(N) = 2.6, an intrinsic rotation Alfven Mach number of M-A similar or equal to 0.02 may be expected from the above deduced scaling, possibly high enough to stabilize resistive wall modes without external momentum input