Resveratrol-Induced Xenophagy Promotes Intracellular Bacteria Clearance in Intestinal Epithelial Cells and Macrophages

Autophagy is a lysosomal degradation process that contributes to host immunity by eliminating invasive pathogens and the modulating inflammatory response. Several infectious and immune disorders are associated with autophagy defects, suggesting that stimulation of autophagy in these diseases should be beneficial. Here, we show that resveratrol is able to boost xenophagy, a selective form of autophagy that target invasive bacteria. We demonstrated that resveratrol promotes in vitro autophagy-dependent clearance of intracellular bacteria in intestinal epithelial cells and macrophages. These results were validated in vivo using infection in a transgenic GFP-LC3 zebrafish model. We also compared the ability of resveratrol derivatives, designed to improve the bioavailability of the parent molecule, to stimulate autophagy and to induce intracellular bacteria clearance. Together, our data demonstrate the ability of resveratrol to stimulate xenophagy, and thereby enhance the clearance of two invasive bacteria involved life-threatening diseases, Salmonella Typhimurium and Crohn's disease-associated Adherent-Invasive Escherichia coli. These findings encourage the further development of pro-autophagic nutrients to strengthen intestinal homeostasis in basal and infectious states

Thrombose veineuse ovarienne et thrombophile (à propos de 13 cas)

Les thromboses veineuses ovariennes (TVO) sont rares et de siège atypique. Les facteurs les favorisant et la place du bilan de thrombophilie sont discutés. Cette étude rétrospective cas-témoin compare les facteurs favorisants, le BT, la survie et les récidives de patientes porteuses de TVO, avec un groupe de patientes, appariées par l'âge, présentant une thrombose veineuse profonde des membres inférieurs (TVP). 13 TVO sont incluses entre 1998 et 2008 au CHU de Clermont-Ferrand, la moyenne est de 2.07 facteurs de risque de thrombose veineuse/patientes ; le post-partum est statistiquement corréléà la survenue de ces thromboses (p=0,016). Le bilan de thrombophilie du groupe TVO n'objective qu'une anomalie majeure (syndrome des antiphospholipides) et 2 anomalies mineures (mutation hétérozygotes Leiden du facteur V) sans différence statistique avec le groupe témoin. Après un suivi moyen de 41 mois pour les TVO versus 39 mois pour les TVP ; et des médianes respectives de traitement anticoagulants de 3 et 6 mois, la mortalité et le taux de récidive sont nuls dans le groupe TVO sans différence statistique avec le groupe TVP. Les TVO sont multifactorielles et ne semblent pas être un mode d'entrée dans la maladie thromboembolique veineuse récidivante. L'absence de complications et l'évolution favorable de TVO non taitées pourraient remettre en cause leur pathogénicité.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

La maladie thromboembolique veineuse, révelatrice d'un cancer ? (quel bilan en 1ère intention chez les patients de plus de 70 ans ?)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

LYMPHOPATHIES ET ANTICORPS ANTI-BETA 2 GLYCOPROTEINE 1 (ETUDE DE 53 PATIENTS)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Syndrome d'Evans (étude rétrospective de 15 cas)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Intérêt d'un bilan systématique à la recherche d'un cancer chez les patients de plus de 70 ans présentant une maladie thromboembolique veineuse (étude prospective)

La réalisation d'un bilan complet systématique à la recherche d'un cancer chez les patients de plus de 70 ans lors du diagnostic de maladie thromboembolique veineuse (MTEV) n'est pas contributive. Un bilan initial simple (examen clinique, hémogramme, créatinine, C réactive protéine, transaminases, radiographie pulmonaire) paraît suffisant en 1ère intention. La fréquence des cancers est de 8% à 12 mois. Les 3 cancers digestifs découverts 7 à 9 mois après la MTEV n'ont pas été dépistés initialement. Il paraît difficile de proposer une endoscopie digestive systématique à cette population fragile surtout en l'absence de point d'appel clinique, biologique ou radiologique, compte tenu des difficultés thérapeutiques et du taux de mortalité élevé.CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Cardiac sarcoidosis: systematic review of literature on corticosteroid and immunosuppressive therapies

International audienceBackground Cardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to review systematically the literature on cardiac sarcoidosis treated by corticosteroids and/or immunosuppressive agents in order to update the management of CS. Methods Using Pubmed, Embase and Cochrane Library databases, we found original articles on corticosteroid and/or standard immunosuppressive therapies for CS which provided at least fair SIGN overall assessment of quality and analyse the relapse rate, major cardiac adverse events (MACEs) and adverse events. We base our methods on Prisma statement and checklist. Results We retrieved 21 studies. Mean quality provided by SIGN assessment was 6.8/14 (range 5–9). Corticosteroids appeared to have a positive impact on left ventricular function, atrioventricular block, and ventricular arrhythmias. For corticosteroids alone, nine (45%) studies (n=351) provided data on relapses, representing an incidence of 34% (n=119). Three studies (14%, n=73) provided data on MACEs (n=33), representing 45% of MACEs in patients treated by corticosteroid alone. Nine studies provided data on adjunctive immunosuppressive therapy in which four studies (n=78) provided data on CS relapse, representing an incidence of 33% (n=26). Limitations consisted in no randomised control trial retrieved and unclear data on MACEs in patients treated by combined immunosuppressive agents and corticosteroids.Conclusions Corticosteroids should be started early after diagnosis but the exact scheme is still unclear. Studies concerning adjunctive conventional immunosuppressive therapies are lacking and benefits of adjunctive immunosuppressive therapies are unclear. Homogenous data on CS long-term outcomes under corticosteroids, immunosuppressive therapies and other adjunctive therapies are lacking

Case report: TNFα antagonists are an effective therapy in cardiac sarcoidosis

International audienceIntroduction: Cardiac sarcoidosis (CS) is a life-threatening disease in which clear recommendations are lacking. We report a case series of CS successfully treated by tumor necrosis factor (TNF)α antagonists. Methods: We conducted a single-center retrospective study of our patients with CS treated by TNFα antagonists. Results: Four cases (4/84, 4.7%) were found in our database. Mean age was 40 years (range 34–53 years), and all were Caucasian men. Mean follow-up was 54.75 months (range 25–115 months). All patients received corticosteroid therapy (CT) and immunosuppressive therapy (IT). TNFα antagonists (infliximab or adalimumab) were started after the first or second CS relapse under CT and IT. One patient experienced relapse under TNFα antagonists (isolated decreased left ventricular ejection) and responded to a shorter interval of TNFα antagonist infusion. CT was discontinued in three patients treated with TNFα antagonists without relapse or major cardiac events during follow-up. No serious adverse event occurred in our case series, possibly due to dose sparing and frequent arrest of CT. Conclusion: TNFα antagonists were effective in refractory and/or relapsing CS treated by corticosteroids and/or immunosuppressive agents, without serious adverse events, and should be considered earlier in CS treatment scheme

Ovarian thrombosis and uterine synechiae after arterial embolization for a late postpartum haemorrhage

International audienc