Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Immune system. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

HIF-2α, but not HIF-1α, promotes iron absorption in mice

Abstract: HIF transcription factors (HIF-1 and HIF-2) are central mediators of cellular adaptation to hypoxia. Because the resting partial pressure of oxygen is low in the intestinal lumen, epithelial cells are believed to be mildly hypoxic. Having recently established a link between HIF and the iron-regulatory hormone hepcidin, we hypothesized that HIFs, stabilized in the hypoxic intestinal epithelium, may also play critical roles in regulating intestinal iron absorption. To explore this idea, we first established that the mouse duodenum, the site of iron absorption in the intestine, is hypoxic and generated conditional knockout mice that lacked either Hif1a or Hif2a specifically in the intestinal epithelium. Using these mice, we found that HIF-1alpha was not necessary for iron absorption, whereas HIF-2alpha played a crucial role in maintaining iron balance in the organism by directly regulating the transcription of the gene encoding divalent metal transporter 1 (DMT1), the principal intestinal iron transporter. Specific deletion of Hif2a led to a decrease in serum and liver iron levels and a marked decrease in liver hepcidin expression, indicating the involvement of an induced systemic response to counteract the iron deficiency. This finding may provide a basis for the development of new strategies, specifically in targeting HIF-2alpha, to improve iron homeostasis in patients with iron disorders.

Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort

Abstract: Brain injury is well established as a cause of early mortality after out-of-hospital cardiac arrest (OHCA), but postresuscitation shock also contributes to these deaths. This study aims to describe the respective incidence, risk factors, and relation to mortality of post-cardiac arrest (CA) shock and brain injury. Retrospective analysis of an observational cohort. 24-bed medical intensive care unit (ICU) in a French university hospital. All consecutive patients admitted following OHCA were considered for analysis. Post-CA shock was defined as a need for infusion of vasoactive drugs after resuscitation. Death related to brain injury included brain death and care withdrawal for poor neurological evolution. None. Between 2000 and 2009, 1,152 patients were admitted after OHCA. Post-CA shock occurred in 789 (68 %) patients. Independent factors associated with its onset were high blood lactate and creatinine levels at ICU admission. During the ICU stay, 269 (34.8 %) patients died from post-CA shock and 499 (65.2 %) from neurological injury. Age, raised blood lactate and creatinine values, and time from collapse to restoration of spontaneous circulation increased the risk of ICU mortality from both shock and brain injury, whereas a shockable rhythm was associated with reduced risk of death from these causes. Finally, bystander cardiopulmonary resuscitation (CPR) decreased the risk of death from neurological injury. Brain injury accounts for the majority of deaths, but post-CA shock affects more than two-thirds of OHCA patients. Mortality from post-CA shock and brain injury share similar risk factors, which are related to the quality of the rescue process.

Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials

Abstract: Background: Tumour necrosis factor α blockers in rheumatoid arthritis are known to increase the risk of serious infections defined as life-threatening, requiring hospitalisation or intravenous antibiotics. Recently, new biological agents have become available. Their safety is an important issue. Purpose: To assess if biological agents, ie rituximab, abatacept and anakinra increase the risk of serious infections in patients with rheumatoid arthritis in published randomised controlled trials. Data source: A systematic review of the literature using PUBMED, EMBASE, Cochrane library and abstracts databases (American College of Rheumatology and European League Against Rheumatism annual meetings) was performed up to October 2007. This search was completed with data from the Food and Drug Administration, the European Agency for the Evaluation of Medicinal Products and manufacturers. Data extraction: Three fixed-effect meta-analyses were performed to compare serious infection rates between each biological agent and placebo. Pooled odds ratios (ORs) were calculated, using the Mantel–Haenszel method with a continuity correction. Data synthesis: Twelve randomised controlled trials with data concerning serious infections were analysed (three for rituximab, five for abatacept and four for anakinra). They included 745 patients, 1960 patients, 2062 patients and 2112 patients treated by rituximab, abatacept, anakinra and placebo respectively. The overall pooled ORs did not reveal a statistically significant increased risk of serious infection for abatacept and rituximab; this risk was increased for high doses of anakinra (⩾100 mg daily) versus low dose and placebo (ORs = 9.63 (95% CI, 1.31 to 70.91) and 3.40 (95% CI, 1.11 to 10.46) respectively). Conclusions: These meta-analyses did not reveal a significant increase in the risk of serious infections during rituximab or abatacept treatments in patients with rheumatoid arthritis; however, high doses of anakinra may increase this risk, especially when patients have comorbidity factors. Large studies must be performed to confirm this safety profile in daily practice.