Post-ischemic cardioprotection by A2A adenosine receptors: dependent of phosphatidylinositol 3-kinase pathway.

Activation of myocardial A2A adenosine receptors during reperfusion has been shown to be cardioprotective. The intracellular mechanisms underlying this protection remain unknown. To understand the beneficial effects of activated A2A adenosine receptors in such a state, we investigated whether the enzymes phosphatidylinositol 3-kinase (PI3K) and caspase-3 can account for this post-ischemic cardioprotective effect in an anesthetized rabbit model of myocardial infarction (30 minutes ischemia; 5 hours reperfusion). Administration of the A2A agonist CGS21680 (0.2 microg/kg/min) 5 minutes before reperfusion began (Early) reduced infarct size expressed as a percentage of the area at risk (25.7 +/- 5.3% versus 46.5 +/- 5.3% for the control group; * P < 0.05). Treatment with the A2A agonist 5 minutes after the onset of reperfusion (Late) had no effect on infarct size (38.2 +/- 6.2%). In the presence of a selective inhibitor of PI3K (LY294002), the beneficial effects of CGS21680 on infarct size was no longer observed (43.9 +/- 7.9%). After 5 hours of reperfusion, higher PI3K activity in the ischemic region was observed in the Early group compared with the other experimental groups. Caspase-3 activity was not observed in these different groups. In another set of experiments, PI3K activity was significantly higher during the first 15 minutes of reperfusion in the Early group as compared with the Control group. Caspase-3 activity increased rapidly during the first 15 minutes of reperfusion in the Control group and remained stable in the Early group. These results indicated that post-ischemic cardioprotection afforded by A2A adenosine receptor activation is PI3K-dependent and modulate rapidly other signaling pathways such as caspase-3

PRISE EN CHARGE DE LA NÉPHRITE LUPIQUE ET DE LA POLYARTHRITE RHUMATOÏDE : QUELLES NOUVEAUTÉS EN 2021 ?

The current standard of care for lupus nephritis has so far been based on sequential immunosuppressive therapy aimed to induce a response, called induction therapy, and to prevent relapse, called maintenance therapy. The results of this approach are deemed unsatisfactory, with only 20-30% of complete renal responses observed at 6-12 months, with at least 20% of patients suffering from chronic kidney failure and 5-20% from end-stage kidney disease at 10 years post-diagnosis. Herein, we have briefly discussed two new treatments, consisting of belimumab and voclosporin, recently registered by drug agencies in the aftermath of controlled trials that demonstrated their superiority given in addition to standard immunosuppressive therapy. Further progress in rheumatoid arthritis is being based on further integrating goals, such as monitoring patients' daily symptoms and well managing comorbidities like cardiovascular disease. An improved understanding of its pathophysiology has enabled translational research designed to develop new therapeutic strategies including numerous targeted biological and synthetic agents. Voici quelques nouveautés importantes dans le domaine de la rhumatologie au cours de l’année 2021. La norme de soins actuelle de la néphrite lupique est basée sur un traitement immunosuppresseur séquentiel destiné à induire une réponse (traitement d’induction) et à éviter les récidives (traitement d’entretien). Les résultats de cette approche ne sont pas suffisamment satisfaisants, avec seulement 20 - 30% de réponse rénale complète à 6 -12 mois, au moins 20% de patients souffrant d’insuffisance rénale chronique et 5 -20% d’insuffisance rénale terminale 10 ans après le diagnostic. Nous discutons brièvement de deux nouveaux traitements, le belimumab et la voclosporine, récemment enregistrés par les agences de médicaments suite à des essais contrôlés qui ont démontré leur supériorité en ajout d’un traitement immunosuppresseur standard. Les progrès engendrés dans le domaine de la polyarthrite rhumatoïde en 2021 reposent sur une meilleure intégration d’objectifs tels que le suivi des symptômes quotidiens des malades et la prise en charge des comorbidités telles que les maladies cardiovasculaires. Une meilleure compréhension de sa physiopathogénie a permis, grâce à la recherche translationnelle, de développer de nouvelles stratégies thérapeutiques incluant de nombreux agents biologiques et synthétiques ciblés

Health-Related Quality of Life in Chronic HCV-Infected Patients Switching to Pegylated-Interferon-Free Regimens (ANRS CO20 CUPIC Cohort Study and SIRIUS Trial)

International audienceObjective We aimed to compare health-related quality of life (HRQL) during and after HCV treatment in patients receiving pegylated-interferon (PEG-IFN)-containing therapy (including boceprevir or telaprevir - ANRS CO20 CUPIC cohort) who subsequently switched to PEG-IFN-free regimens (sofosbuvir + ledipasvir with or without ribavirin (RBV) - SIRIUS trial).Methods Two analyses were performed. The first compared physical (PCS) and mental (MCS) HRQL (MOS SF-12) scores during treatment between CUPIC and SIRIUS. The second compared PCS and MCS scores after treatment end between CUPIC and SIRIUS. The analyses used linear regression mixed models adjusted for pre-treatment HRQL scores, gender and age at each visit.Results Among patients enrolled successively in both studies, 43 (corresponding to 212 HRQL assessments) and 43 (82 HRQL assessments) were eligible for the “during” and “post" treatment analyses, respectively. In the “during-treatment” analysis, we found both significantly higher PCS and MCS values during PEG-IFN-free treatment than for PEG-IFN-containing treatment. In the “post-treatment” analysis, results showed significantly higher MCS values after PEG-IFN-free treatment than after PEG-IFN-containing treatment. No significant difference was found for PCS in “post-treatment analysis”.Conclusions These results highlight an improvement in both physical and mental HRQL during HCV treatment, but no major improvement in physical HRQL after treatment end, when comparing PEG-IFN-free regimens with PEG-IFN-containing regimens. This suggests that in the PEG-IFN-free regimens era, screening and comprehensive care of comorbidities and residual somatic symptoms during treatment, and especially after HCV clearance, are still needed to improve patient outcomes