The intracellular tyrosine residues of the ATP-gated P2X(1) ion channel are essential for its function.

In this study, we mutated the four highly conserved intracellular tyrosine residues of the P2X(1) ion channel were mutated into phenylalanine. Simultaneous electrophysiological and calcium measurements in transfected human embryonic kidney (HEK 293) cells indicated that Y362F and Y370F mutants were non-functional, despite their proper plasma membrane expression. The Y16F and Y363F mutants retained 2.2% and 26% of the wild-type P2X(1) activity, respectively. However, no tyrosine phosphorylation was detected on Western blots of P2X(1) immunoprecipitates derived either from HEK 293 cell lysates or from human platelets, expressing P2X(1) endogenously. Thus, Y16, Y362, Y363 and Y370 are required for the appropriate three-dimensional structure and function of the intracellular P2X(1) domains

La dureté du blé a-t-elle une influence sur la dépense énergétique à la mouture?Topo donnant suite à une question de Bernard Rolland, INRAE

International audienceLa dureté du blé at -elle une influence sur la dépense énergétique à la mouture 07-08/03/2023 / Changins (Suisse) / V. Lullien La dureté du blé at -elle une influence sur la dépense énergétique à la mouture? Topo donnant suite à une question de Bernard Rollan

Pretreatment with P2Y12 inhibitors and outcome in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention

International audienceAIMS:Preload with clopidogrel, ticagrelor, or prasugrel in the setting of ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) is frequently applied. Limited data are available regarding the outcome impact of pretreatment with these drugs in the real world.METHODS AND RESULTS:The outcome of 760 STEMI patients treated by primary PCI receiving clopidogrel, prasugrel, or ticagrelor (n = 269, 327, 164, respectively) was evaluated. Patients in the clopidogrel group were older, whereas those in the ticagrelor group had less hypertension but were more active smokers. Angiographic characteristics were comparable among the three groups. At 1 month, more events were observed in the clopidogrel group (11.1%) than in the ticagrelor and prasugrel groups (7.1 vs. 5.1%, P = 0.025), whereas the number of events in the ticagrelor and prasugrel groups did not differ. At 1 year, similar differences existed, mainly driven by a higher rate of death (19.5%, P = 0.008) or stent thrombosis (2 vs. 1.3% for ticagrelor, P = 0.132; vs. 0.3% for prasugrel, P = 0.07) in the clopidogrel group. In-hospital and 1-year bleeding rates were similar between groups.CONCLUSION:In real-world practice, pretreatment with prasugrel or ticagrelor in ongoing STEMI treated by primary PCI seems to be a well tolerated alternative strategy compared with clopidogrel but provides superior benefit in terms of outcomes

Perinatal mortality and morbidity, timing and route of delivery in monoamniotic twin pregnancies: a retrospective cohort study

International audiencePurpose Monoamniotic twin pregnancies are at high risk of perinatal complications and fetal loss. The objective of this study is to describe the management and outcomes of monoamniotic twin pregnancies in a French university obstetrics department. Methods Retrospective review of all consecutive monoamniotic twin pregnancies managed between 1992 and 2018 in a level-3 university hospital maternity unit. Antenatal variables, gestational age and other neonatal characteristics at delivery, mode of delivery, and its reason were recorded, together with outcomes, including a composite adverse neonatal outcome. Results Overall, 46 monoamniotic twin pregnancies (92 fetuses) were identified during the study period. Among them, 27 fetal losses and 2 early neonatal deaths were reported. Congenital abnormalities accounted for 33.3% of the 27 fetal losses, and unexpected fetal deaths for 29.6%. Among the 37 women who gave birth to 65 live infants at 23 or more weeks of gestation, 17 had cesarean and 19 vaginal deliveries. Overall and composite adverse neonatal outcomes did not differ significantly for the 33 children born vaginally and the 31 by cesarean deliveries. The prospective risk of intrauterine death in all 92 fetuses reached its nadir of 1.8% at 33(6/7) weeks. Conclusion This series confirms the still high risk of fetal and neonatal death of these twins and shows that congenital abnormalities but also unexpected fetal deaths account for the majority of pre- and postnatal mortality. Our data suggest that vaginal delivery of monoamniotic twins is safe and that delivery for uncomplicated monoamniotic twins should be considered around 33 weeks of gestation, but not later than 35 weeks

A natural dominant negative P2X1 receptor due to deletion of a single amino acid residue.

We describe a naturally occurring dominant negative P2X1 mutant. This mutant lacks one leucine within a stretch of four leucine residues in its second transmembrane domain (TM2) (amino acids 351-354). Confocal microscopy revealed proper plasma membrane localization of the mutant in stably transfected HEK293 cells. Nevertheless, voltage-clamped HEK293 cells expressing mutated P2X1 channels failed to develop an ATP or ADP-induced current. Furthermore, when co-expressed with the wild type receptor in Xenopus oocytes, the mutated protein exhibited a dose-dependent dominant negative effect on the normal ATP or ADP-induced P2X1 channel activity. These data indicate that deletion of a single apolar amino acid residue at the inner border of the P2X1 TM2 generates a nonfunctional channel

Early inflammation in the airways of a cystic fibrosis foetus

In cystic fibrosis patients, inflammation is often considered to be secondary to chronic infections. In the present study, we show increased levels of pro-inflammatory proteins in the lungs of a cystic fibrosis foetus compared to the lungs of two normal foetuses. Our findings suggest therefore the existence of an early intrinsic pro-inflammatory state in cystic fibrosis airways. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved

Early thrombogenicity of coronary stents: comparison of bioresorbable polymer sirolimus-eluting and bare metal stents in an aortic rat model.

Although 1-month dual antiplatelet therapy (DAPT) in patients treated with bare metal stents (BMS) is well established, the optimal duration of DAPT after implantation of a drug-eluting stent (DES) is still a matter of debate. The safety of shortened DAPT is under investigation due to concern about the risk of stent thrombosis. Data on platelet activation and prothrombotic response in vivo following bioresorbable polymer sirolimus-eluting stent (BP-SES) implantation are scarce. The aim of our study was to compare the early thrombogenicity of BP-SES with that of BMS in an aortic rat model. Overall, 30 rats underwent stent implantation in the abdominal aorta: BMS (Pro-Kinetic Energy; N=15) and BP-SES (Ultimaster Tansei; N=15) were compared in terms of their early thrombogenicity. CD62P exposure at the platelet surface and fibrinogen binding at the integrin receptor were not different between BMS and BP-SES over time. The thrombus coverage of the scaffold (0 vs. 0.1%, P=0.84) was similarly low in both groups at Day 28; thrombotic deposits had totally disappeared at Day 84. The endothelial strut coverage was similarly high at 1 month (90 vs. 95%, P=0.64) and 3 months (87 vs. 97%, P=0.99) following BMS and BP-SES implantation, respectively. This study demonstrates the low early thrombogenicity of a BP-SES implanted in an aortic rat model, which did not differ from a BMS. These data could be helpful to support the safety of a shortened 1-month DAPT duration following BP-SES implantation in the human coronary artery

Belgian clinical guidance on anticoagulation management in hospitalised and ambulatory patients with COVID-19

OBJECTIVES: COVID-19 predisposes patients to thrombotic disease. The aim of this guidance document is to provide Belgian health-care workers with recommendations on anticoagulation management in COVID-19 positive patients. METHODS: These recommendations were based on current knowledge and a limited level of evidence. RESULTS: We formulated recommendations for the prophylaxis and treatment of COVID-related venous thromboembolism in ambulatory and hospitalised patients, as well as recommendations for the use of antithrombotic drugs in patients with prior indication for anticoagulation who develop COVID-19. CONCLUSIONS: These recommendations represent an easy-to-use practical guidance that can be implemented in every Belgian hospital and be used by primary care physicians and gynaecologists. Of note, they are likely to evolve with increased knowledge of the disease and availability of data from ongoing clinical trials.status: publishe