Phytalgic®, a food supplement, vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial

International audienceINTRODUCTION: The medicinal treatment of osteoarthritis (OA) is mostly symptomatic to relieve pain and incapacity with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), drugs with well-known risks. Complementary medicines might reduce the symptoms of OA and decrease the need for NSAIDs. This study tested the effects of a food supplement, Phytalgic, on pain and function in patients with osteoarthritis and their use of analgesic and NSAIDs. METHODS: A randomized double-blind parallel-groups clinical trial compared Phytalgic (fish-oil, vitamin E, Urtica dioica) to a placebo for three months, in 81 patients with OA of the knee or hip using NSAIDs and/or analgesics regularly. The main outcome measures were use of NSAIDs (in Defined Daily Doses per day - DDD/day) or analgesics (in 500 mg paracetamol-equivalent tablets per week (PET/week) measured each month, and Western Ontario-McMaster University Osteo-Arthritis Index (WOMAC) function scales. RESULTS: After three months of treatment, the mean use of analgesics in the active arm (6.5 PET/week) vs. the placebo arm (16.5) was significantly different (P < 0.001) with a group mean difference of -10.0 (95% CI: -4.9 to -15.1). That of NSAIDs in the active arm (0.4 DDD/day) vs the placebo arm (1.0 DDD/day) was significantly different (P = 0.02) with a group mean difference of - 0.7 DDD/day (95% CI: -0.2 to -1.2). Mean WOMAC scores for pain, stiffness and function in the active arm (respectively 86.5, 41.4 and 301.6) vs the placebo arm (resp. 235.3, 96.3 and 746.5) were significantly different (P < 0.001) with group mean differences respectively of -148.8 (95% CI: -97.7 to -199.9), -54.9 (95% CI: -27.9 to -81.9) and -444.8 (95% CI: -269.1 to -620.4). CONCLUSIONS: The food supplement tested appeared to decrease the need for analgesics and NSAIDs and improve the symptoms of osteoarthritis. TRIAL REGISTRATION: Clinicaltrials.gov NCT00666523

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

Mécanismes d'interaction entre les mastocytes et les cellules musculaires lisses bronchiques dans l'asthme

L'inflammation des voies aériennes dans l'asthme comporte une localisation de mastocytes (MC) dans la couche musculaire lisse bronchique. L'objectif de ce travail est d'explorer les mécanismes régissant l'interaction MC-cellules musculaires bronchiques (CML). En réponse à des stimuli pro-inflammatoires (tryptase, TNF-a), les CML attirent les MC par leur production de TGF-ß1, SCF et fractalkine. L'effet de la tryptase implique le PAR-2 et les MAP kinases. Les MC adhèrent aux CML via la matrice extracellulaire par une liaison CD44-collagène type I. La myosite mastocytaire est corrélée avec l'expression de TGF-ß1 et CD44 par le muscle lisse bronchique, l'infiltration mastocytaire du muscle lisse bronchique, l'hyperactivité bronchique et le dépôt bronchique de collagène sont fortement diminués chez les souris asthmatiques CD44v6/v7-/-. La coopération MC-CML contribue au remodelage des voies aériennes. CD44v6 représente une cible thérapeutique potentielle dans l'asthme allergique chronique.The number of mast cells infiltrating the bronchial smooth muscle is higher in asthmatic patients and closely related with airways inflammation. We have thus examined the potential for interaction between hhumain airway smooth muscle cells (HASMCs) and mast cells. Stimulation of HASMCs by tryptase or TNF-a can induce mast cell chemotaxis through production of RGF-b1, SCF and fractalkine. The tryptase effect depends on PAR-2 activation and MAP kinases pathway. Mast cells adhesion to HASMCs involves adhesion molecule CD44 and components of the extracellular matrix, such as collagen type I a1. The number of mast cells within the smooth muscle layer of asthmatic patients was related to TGF-b1 and CD44 expression by smooth muscle. In a mouse model of chronic asthma, mast cells infiltration, bronchial hyperreactivity and collagen deposition in bronchi were strongly decreased in asthmatic CD44v6/v7-/- mice. The autoactivation loop involving mast cells and HASMC could contribute to airway remodelling. CD44v6 represents a potentially attractive target for asthma therapy.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Prebreakdown and Breakdown in Liquid Nitrogen under Pulsed Heating for Superconducting Applications

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Influence of Subcooling on Breakdown and Prebreadown in Heated Liquid Nitrogen

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Prebreakdown and Breakdown in Liquid Nitrogen under Pulsed Heating for Superconducting Applications

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Claquage dans l'azote liquide sous chauffage pulsé, et application aux limiteurs supraconducteurs HVDC

International audienceUne étude expérimentale des phénomènes de claquage et de pré-claquage dans l'azote liquide (LN2) est réalisée, dans le but d'apporter des données utiles pour la conception de systèmes supraconducteurs haute tension. Un ruban métallique soumis à un chauffage pulsé est utilisé pour simuler les conditions de fonctionnement d'un appareil supraconducteur lors d'une transition supraconducteur/résistif. Les mesures des tensions de claquage entre le ruban et une électrode plane montrent la forte influence de la polarité du ruban, de la température du LN2 et du délai entre le chauffage et l'application de la tension. Des visualisations obtenues avec une caméra à haute vitesse permettent de caractériser la séquence d'événements de pré-claquage : ébullition du liquide, développement de bulles de vapeur ionisées, et propagation d'un streamer