0000000000082733
AUTHOR
M. Dumas
Dose-dependent biphasic leptin-induced proliferation is caused by non-specific IL-6/NF-κB pathway activation in human myometrial cells
Background and Purpose Leptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour (PTL), as it is able to prevent in vitro uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence. Experimental Approach We stimulated human primary myometrial smooth muscle cells with leptin in the presence or …
Stimulation of the ADRB3 Adrenergic Receptor Induces Relaxation of Human Placental Arteries: Influence of Preeclampsia1
Preeclampsia, which complicates 3-8% of pregnancies, is one of the leading causes of neonatal morbidity and mortality. Its pathophysiology remains unclear. The aim of the present study was to investigate the presence and the role of beta2- and beta2-adrenergic receptors (ADRB2 and ADRB3, respectively) in human placental arteries and to assess the influence of preeclampsia on ADRB responsiveness. SR 59119A, salbutamol, and isoproterenol (ADRB3, ADRB2, and nonselective ADRB agonists, respectively) induced a concentration-dependent relaxation of placental artery rings obtained from women with uncomplicated or preeclamptic pregnancies. SR 59119A-induced relaxation was unaffected by the blockade…
Effects of Leptin on Lipopolysaccharide-Induced Remodeling in an In Vitro Model of Human Myometrial Inflammation1
Reorganization of myometrial extracellular matrix (ECM) is essential for the uterus to achieve powerful synchronous contractions during labor. Remodeling of the ECM has been implicated in membrane rupture and cervical ripening. Because maternal obesity is associated with both delivery disorders and elevated circulating leptin levels, this study aimed to assess the ability of leptin to interfere with lipopolysaccharide (LPS)-induced myometrial ECM remodeling. Myometrial biopsy samples were obtained from women undergoing cesarean delivery before labor onset. Myometrial explants were incubated for 48 h with LPS and leptin. LPS challenge was associated with a marked decrease in collagen content…
Cémiplimab et carcinomes épidermoïdes cutanés localement évolués ou métastatiques : premières données de vie réelle
Introduction Dans l’essai de phase 2 evaluant le cemiplimab (CEM) chez des patients (pts) ayant un carcinome epidermoide cutane (CEC) localement evolue ou metastatique, le taux de meilleure reponse (TMR) etait de 47 % et la survie globale (SG) a un an de 81 %. Une autorisation temporaire d’utilisation (ATU) nominative a permis a ces pts d’acceder au CEM hors protocole. Notre objectif etait d’analyser les donnees d’efficacite et de tolerance de cette ATU. Materiel et methodes Les 58 centres ayant inclus des pts entre le 08/18 et le 10/19 dans cette etude retrospective ont ete sollicites pour completer une fiche standardisee par pt. L’objectif principal etait le TMR, les objectifs secondaires…
Functional, biochemical and molecular biological evidence for a possible β3-adrenoceptor in human near-term myometrium
The possible existence of a β3-adrenoceptor (β3-AR) in human near-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the β3-AR), salbutamol and terbutaline (β2-AR agonists) each produced a concentration-dependent relaxation of the myometrial spontaneous contractions. There were no differences in pD2 values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR 59104A>terbutaline∼salbutamol∼CGP 12177 (Emax=52±7%, 42±12% and ∼ 30% respectively). …