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 …

Pharmacokinetic evaluation of esomeprazole for the treatment of gastroesophageal reflux disease

Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases such as gastroesophageal reflux disease (GERD). They are recommended by the American College of Gastroenterology for healing erosive esophagitis (EO) and as long-term treatment in patients with healed EO. The available PPIs differ somewhat in their pharmacokinetics and clinical properties, but whether these differences are of clinical relevance is a matter of debate. Some safety concerns have been raised with the use of PPIs, mostly an increased incidence of infectious diseases such as community-acquired pneumonia or Clostridium difficile diarrhea.This article explores the results of clinical studies on…

Pantoprazole: from drug metabolism to clinical relevance.

Conditions requiring inhibition of acid secretion, such as gastro-oesophageal reflux disease (GORD), peptic ulcers, non-ulcer dyspepsia or the use of NSAIDs, are very common, and their prevalence is expecting to rise as they are seen predominantly amongst the elderly. Among the drugs available to inhibit acid secretion, proton pump inhibitors (PPI) have been shown to have the best efficacy-safety ratio and have been used widely.This paper was intended to provide an overall presentation of one of these PPIs, pantoprazole.This study was first intended to give an overview of pantoprazole, so a Medline search was conducted using pantoprazole as unique search term, without publication date restr…

Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial

SummaryBackground A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). Aim To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. Methods Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300–500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. Results Twenty-one patients were enrolled, inclu…

Treatment of pancreatic cancer: A narrative review of cost-effectiveness studies.

Cancer of the pancreas is the second most frequent digestive cancer in the US, accounting for about 44,000 new cases per year. In Europe, it is the sixth most frequent cancer, accounting for 2.8% of cancers in men and 3.2% in women. With a five-year survival of less than 10%, it is the fifth leading cause of cancer-related death. The majority of cases are diagnosed above the age of 65 and in about 60% of cases at an advanced stage, explaining that little improvement has been observed in survival over the past 30 years. Radical surgery offers the only curative treatment of pancreatic cancer. Alternative or combined therapeutic options in particular consist of adjuvant or neoadjuvant chemothe…

Cancer relapse under chemotherapy: why TLR2/4 receptor agonists can help.

Liver or lung metastases usually relapse under chemotherapy. Such life-threatening condition urgently needs new, systemic anticancer compounds, with original and efficient mechanisms of action. In B16 melanoma mice treated with cyclophosphamide, D'Agostini et al. [D'Agostini, C., Pica, F., Febbraro, G., Grelli, S., Chiavaroli, C., Garaci, E., 2005. Antitumour effect of OM-174 and Cyclophosphamide on murine B16 melanoma in different experimental conditions. Int. Immunopharmacol. 5, 1205-1212.] recently found that OM-174, a chemically defined Toll-like receptor(TLR)2/4 agonist, reduces tumor progression and prolongs survival. Here we review 149 articles concerning molecular mechanisms of TLR2…

Antitumoral Effects of Lipids A, Clinical Studies

Cancer remains the second leading cause of death, after cardiovascular diseases, in industrialized countries. The first goal to achieveis to prevent cancer occurrence or to diagnose it at an early and curable stage. Some screening strategies have been developed, with controversies across countries, for several cancer type; colorectal, breasts or prostate cancer for example.

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…

Incident use of proton pump inhibitors in France, 2015

IF 2.314; International audience

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…

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 pat…

Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors.

International audience; BACKGROUND: Lipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was cond…

Relative risk rather than absolute risk reduction should be preferred to sensitise the public to preventive actions.

We thank Lawrence and colleagues1 for their interest in our work,2 about which they raised some comments as the need of expressing results in absolute rather than relative risks. As they appropriately mentioned in their correspondence, absolute risk is an important parameter for the estimation of the effect of an intervention and must sometimes be preferred to relative risk. However, when discussing with health professionals and policymakers, using absolute risk reductions, expressed as percentages, may incorrectly lead to an intervention being considered unnecessary. As example, what would be the point of reducing by 30% the occurrence of an event affecting 2% of the population? This is ex…

Relevance of new recommendations on routine antenatal prevention of rhesus immunization: an appraisal based on a retrospective analysis of all cases observed in two French administrative areas of 3 million inhabitants.

Abstract Objective To assess the potential impact of new guidelines recommending routine antenatal prophylaxis at 28 weeks of pregnancy on incidence, consequences and cost of rhesus immunization. Study design All rhesus immunizations of 224,500 ongoing pregnancies in two neighbouring administrative areas in France between 2000 and 2006 were enrolled in this retrospective study. To determine the aetiology of immunization and to specify when sensitization occurred, we searched sensitizing events between the last negative and the first positive red-cell antibody test results. Perinatal consequences and costing were also analyzed. Results From 138 rhesus negative women bearing anti-D antibodies…

Accuracy of blood transfusion in postpartum hemorrhage to assess maternal morbidity.

International audience; OBJECTIVE: To measure the accuracy of blood transfusion (timing and number of blood units) in postpartum hemorrhage (PPH) in a perinatal network. STUDY DESIGN: (1) The ANONYMAT software system was used for anonymization and linkage of two large stand-alone databases, the Burgundy Perinatal Network (BPN) and the National Blood Centre (EFS) databases, which contain, respectively, clinical data from hospital discharges and information concerning any blood transfusion in France (considered as the gold standard database for identifying any transfusion). (2) Identification of prescriptions of at least one red blood cell (RBC) unit at the day of delivery (≥22 weeks) and up …

The human near-term myometrialβ3-adrenoceptor but not theβ2-adrenoceptor is resistant to desensitisation after sustained agonist stimulation

1. In order to compare the beta(2)- and beta(3)-adrenoceptor (beta-AR) desensitisation process in human near-term myometrium, we examined the influence of a pretreatment of myometrial strips with either a beta(2)- or a beta(3)-AR agonist (salbutamol or SR 59119A, respectively, both at 10 microm, for 5 and 15 h) on the relaxation and the cyclic adenosine monophosphate (cAMP) production induced by these agonists. 2. To assess some of the mechanisms potentially implicated in the beta-AR desensitisation process, we studied the influence of such treatment on the number of beta(2)- and beta(3)-AR binding sites, the beta(2)- and beta(3)-AR transcripts expression and the phosphodiesterase 4 (PDE4) …

Changes in Maternal Blood Inflammatory Markers As a Predictor Of Chorioamnionitis: A Prospective Multicenter Study

Problem To evaluate the inflammatory pattern in maternal circulation from women with preterm premature rupture of membranes (PPROM) considering the occurrence of histologically confirmed chorioamnionitis (HCA). Method of study A prospective study was conducted in 121 women with PPROM between 24 and 34 + 0 weeks of gestation. Association between white blood cells (WBC) count, plasma CRP, IL-6, MCP-1 and IP-10 levels, and HCA was assessed. Results The rate of HCA was 44.7% (54/121). During the 5 days preceding delivery, median CRP, WBC, and IL-6 levels were significantly higher in the HCA than in no-HCA group (P < 0.001). Variations in IL-6, IP-10 levels, during the 24–72 hr before delivery, …

Dexlansoprazole Delayed Release: Pharmacotherapy of Erosive Esophagitis and GERD

Dexlansoprazole MR is a modified release formulation of the R-enantiomer of lansoprazole, which employs a novel Dual Delayed Release (DDR) technology. Pharmacokinetic studies have shown that the DDR technology provides a two peaks drug release, accuring 1–2 hours and 4–5 hours after dosing, leading to an extended duration of therapeutic plasma drug concentrations compared with conventional delayed release lansoprazole. Dexlansoprazole MR 30 and 60 mg provided superior intragastric pH control compared to that obtained with lansoprazole 15 mg and 30 mg once daily dosing. Dexlansoprazole can be taken without regard to food. The drug has been shown to be as efficacious as lansoprazole in heali…

PGI19 Stress Ulcer Bleeding Prophylaxis with Proton Pump Inhibitors, H2 Receptor Antagonists or Sucralfate: A Cost-Effectiveness Analysis

Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-alpha on oligodendrocytes and astrocytes

X-linked adrenoleukodystrophy (X-ALD) is characterized by ABCD1 deficiency. This disease is associated with elevated concentrations of very long chain fatty acids (C24:0 and C26:0) in the plasma and tissues of patients. Under its severe form, brain demyelination and inflammation are observed. Therefore, we determined the effects of C24:0 and C26:0 on glial cells:oligodendrocytes, which synthesize myelin, and astrocytes, which participate in immune response. So, 158N murine oligodendrocytes, rat C6 glioma cells, rat primary cultures of neuronal-glial cells, and of oligodendrocytes were treated for various periods of time in the absence or presence of C24:0 and C26:0 used at plasmatic concent…

The human near-term myometrial beta 3-adrenoceptor but not the beta 2-adrenoceptor is resistant to desensitisation after sustained agonist stimulation.

International audience; 1. In order to compare the beta(2)- and beta(3)-adrenoceptor (beta-AR) desensitisation process in human near-term myometrium, we examined the influence of a pretreatment of myometrial strips with either a beta(2)- or a beta(3)-AR agonist (salbutamol or SR 59119A, respectively, both at 10 microm, for 5 and 15 h) on the relaxation and the cyclic adenosine monophosphate (cAMP) production induced by these agonists. 2. To assess some of the mechanisms potentially implicated in the beta-AR desensitisation process, we studied the influence of such treatment on the number of beta(2)- and beta(3)-AR binding sites, the beta(2)- and beta(3)-AR transcripts expression and the pho…

Pharmacokinetic and clinical evaluation of esomeprazole and ASA for the prevention of gastroduodenal ulcers in cardiovascular patients.

Low-dose aspirin (ASA, 75 - 325 mg/day) is widely used for the primary and secondary prevention of cardiovascular (CV) diseases. However, the value of primary prevention ASA is uncertain as the reduction in occlusive events needs to be weighed against the significant increase in major bleedings. Prevention with antisecretory drugs has been proposed to reduce the incidence of ASA-induced gastrointestinal (GI) bleedings, but non-adherence to gastro-protection is of concern, as it significantly increases the risk of upper GI adverse events. Beside patients and physicians education, one approach to overcome non-adherence is the development of fixed-dose combination.This review explores the resu…

Failure to renew prescriptions for gastroprotective agents to patients on continuous nonsteroidal anti-inflammatory drugs increases rate of upper gastrointestinal injury.

Patients with risk factors for gastrointestinal (GI) disorders who continuously use nonsteroidal anti-inflammatory drugs (NSAIDs) also should take gastroprotective agents (GPAs), such as proton pump inhibitors (PPIs). However, it is not clear how many physicians continue to prescribe GPAs to these patients, and whether stopping the GPA prescription increases GI complications.We performed a retrospective, observational, longitudinal study using a validated electronic database of representative general practitioners in France. We analyzed data for 1856 patients at risk for GI events (65 y, past history of GI ulcer, or receiving antiplatelet agents) who received prescriptions for an NSAID and …

Effects of leptin on lipopolysaccharide-induced myometrial apoptosis in an in vitro human model of chorioamnionitis.

Objective This study was aimed at assessing the role of leptin on human myometrium, by studying its receptor expression in pregnant myometrium and the interaction of leptin with inflammation-induced apoptosis. Study Design Myometrial samples were obtained from women with uncomplicated pregnancies who underwent cesarean delivery at term before labor onset. The effect of leptin on apoptosis was assessed by the incubation of myometrial strips with leptin (10 –10 to 10 –8 mol/L; 48 hours) before lipopolysaccharide treatment (10 μg/mL; 48 hours). Results Long and short leptin receptor isoforms were expressed in myometrial cells of pregnant women. Leptin prevented lipopolysaccharide-induced apopt…

Biphasic Erk1/2 activation sequentially involving Gs and Gi signaling is required in beta3-adrenergic receptor-induced primary smooth muscle cell proliferation

Abstract The beta3 adrenergic receptor (B3-AR) reportedly induces cell proliferation, but the signaling pathways that were proposed, involving either Gs or Gi coupling, remain controversial. To further investigate the role of G protein coupling in B3-AR induced proliferation, we stimulated primary human myometrial smooth muscle cells with SAR150640 (B3-AR agonist) in the absence or presence of variable G-protein inhibitors. Specific B3-AR stimulation led to an Erk1/2 induced proliferation. We observed that the proliferative effects of B3-AR require two Erk1/2 activation peaks (the first after 3 min, the second at 8 h). Erk1/2 activation at 3 min was mimicked by forskolin (adenylyl-cyclase a…

Prevalence and Incidence of Subclinical Proximal Tubulopathy (SPT) over 96 Weeks in Chronic Hepatitis B (CHB) Patients Treated with Entecavir (ETV) or Tenofovir Disoproxil (TDF) without Renal Insufficiency (RI) or Hypophosphatemia during the Follow-up

International audience

Compassionate use of everolimus for refractory epilepsy in a patient with MTOR mosaic mutation

Abstract The MTOR gene encodes the mechanistic target of rapamycin (mTOR), which is a core component of the PI3K-AKT-mTOR signaling pathway. Postzygotic MTOR variants result in various mosaic phenotypes, referred to in OMIM as Smith-Kinsgmore syndrome or focal cortical dysplasia. We report here the case of a patient, with an MTOR mosaic gain-of-function variant (p.Glu2419Lys) in the DNA of 41% skin cells, who received compassionate off-label treatment with everolimus for refractory epilepsy. This 12-year-old-girl presented with psychomotor regression, intractable seizures, hypopigmentation along Blaschko's lines (hypomelanosis of Ito), asymmetric regional body overgrowth, and ocular anomali…

Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years

ObjectiveThe incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years.DesignData on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change.ResultsWe retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On averag…

Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways.

We aimed to investigate the role of K(+) channels and nitric oxide (NO) on the relaxant effects of arachidonic acid in the human intralobar pulmonary arteries. Arachidonic acid produced a concentration-dependent relaxation (E(max)=93+/-3% of maximal relaxation induced by papaverine 0.1 mM;-log EC(30)=7.03+/-0.09) that was antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17-octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase inhibition and NO synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l-NOARG, 100 microM), by the simultaneous inhibition of CYP and …

Kosaki overgrowth syndrome: A novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications

Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long-term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contrac…

Est-il possible de construire un indicateur de morbidité maternelle sévère (hémorragie maternelle) à partir des données du programme de médicalisation des systèmes d’information complétées par celles de l’Établissement français du sang ?

Is routine second-look endoscopy effective after endoscopic hemostasis in acute peptic ulcer bleeding? A meta-analysis

Background Routine second-look endoscopy in modern-era peptic ulcer bleeding (PUB) remains controversial. Objective To assess the effectiveness of routine second-look endoscopy in patients with PUB exhibiting high-risk stigmata after standard medical care and endoscopic therapy. Design Comprehensive literature searches (1990-2011) were performed, seeking randomized trials comparing a routine with an as-needed second endoscopy. Main Outcome Measurements The main outcome was rebleeding. Secondary outcomes were surgery and mortality. Subanalyses assessed the influence of study quality, rebleeding definitions, endoscopic hemostasis modality, and proton pump inhibitor (PPI) therapies. Analyses w…

Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?

International audience; The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the beta3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predo…

Validation des hémorragies maternelles codées dans le programme de médicalisation des systèmes d’information (PMSI) par couplage aux données de l’Établissement français du sang (EFS)

Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy

AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…

Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives. A review of the literature

IF 2.004 (2017); International audience; With the development of next generation sequencing, beyond identifying the cause of manifestations that justified prescription of the test, other information with potential interest for patients and their families, defined as secondary findings (SF), can be provided once patients have given informed consent, in particular when therapeutic and preventive options are available. The disclosure of such findings has caused much debate. The aim of this work was to summarize all opinion-based studies focusing on SF, so as to shed light on the concerns that this question generate. A review of the literature was performed, focusing on all PubMed articles repo…

Prévention des complications digestives des anti-inflammatoires non stéroïdiens : de la connaissance des facteurs de risque à leur prise en compte

Resume Les anti-inflammatoire non steroidiens (AINS) representent une classe medicamenteuse tres largement prescrite pour deux raisons principales, le vieillissement de la population qui augmente la prevalence de certaines indications cibles comme l’arthrose et surtout leur efficacite qui en fait une classe medicamenteuse indispensable. On estime qu’en France 25 a 30 millions de prescriptions, chaque annee, comportent un AINS. Neanmoins, leur utilisation est limitee par leur profil de tolerance, en particulier digestif, qui en fait une des principales causes d’hemorragie digestive du tractus superieur d’origine ulcereuse. Bien que plus souvent negligee, la toxicite digestive basse est reell…

Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding

*Division of Gastroenterology, and Division of Clinical Epidemiology, McGill University and the McGill University Health Centre, Montreal, Quebec, Canada; INSERM IC-P 803, CHU du Bocage, Dijon, France; Universite de Bourgogne, Dijon, France; **Department of Medicine, Division of Gastroenterology, Farncombe Family igestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Guelph General Hospital, Guelph and McMaster University, Guelph, Ontario, Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Division of Gastroenterology, Medical University Canada; f South Carlolina, Charleston, South Carolina; and the Departmen…

Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPHoxidase activity and induces catalase expression via PPARγ activation

IF 4.521; International audience; The beta3 adrenergic receptor (β3-AR) stimulation plays a protective role against preterm labor by blocking myometrial contraction, cytokine production, remodeling and apoptosis. We previously demonstrated that macrophage-induced ROS production in the myometrium was a key element leading to the induction of all these labor-associated features. We thus aimed to investigate if the β3-AR could be expressed in human macrophages and could trigger its protective role in the myometrium by directly inhibiting ROS production. Using lipopolysaccharide (LPS)-stimulated myometrial samples and cell co-culture experiments, we demonstrated that β3-AR stimulation inhibits …

Systematic review: the presenting international normalised ratio (INR) as a predictor of outcome in patients with upper nonvariceal gastrointestinal bleeding

Aliment Pharmacol Ther 2011; 33: 1010–1018 Summary Background  The prognostic value of an elevated international normalised ratio (INR) as part of initial risk stratification in nonvariceal upper gastrointestinal bleeding (NVUGIB) remains poorly characterised. Aim  To assess the usefulness of the initial INR in patients with NVUGIB. Method  After a systematic review, we included the presenting INR and other validated prognosticators in multivariable models predicting rebleeding and mortality. Data are reported as odd ratios and 95% confidence intervals. Results  Only two of 769 candidate studies were useful, but reported disparate, highly selected NVUGIB patients with varying threshold init…

Cost-Effectiveness Analysis: Stress Ulcer Bleeding Prophylaxis with Proton Pump Inhibitors, H2 Receptor Antagonists

Abstract Objectives Proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) present varying pharmacological efficacy in preventing stress ulcer bleeding (SUB) in intensive care units. The literature also reports disparate rates of ventilator-assisted pneumonia (VAP) as side effects of these treatments. We compared the cost-effectiveness of these two prophylactic pharmacological options. Methods We constructed a decision tree with a 60-day time horizon for patients at high risk for developing SUB, receiving either PPIs or H2RAs. For each treatment strategy, patients could be in one of three states of health: SUB, VAP, or no complication. Contemporary, clinically relevant probabilit…

Simulation et éducation thérapeutique : jamais sur soi (ou les siens) la première fois!

[Extraits de l'introduction] Grâce au developpement technologique, il est possible de creer des environnements fictifs avec plus ou moins de fidelite par rapport a la realite des soins. Ces environnements reconstitues permettent ce que l'on appelle la simulation qui est une technique pedagogique permettant le developpement de competences, de savoir-faire et d'habiletes constitutives de tâches professionnelles pour lesquelles un enseignement direct s'avere impossible pour des raisons deontologiques (securite et surete du patient et du soignant), economique (cout du materiel) ou technique (tres faible probabilite d'occurrence des incidents ou accidents) [1]. L'objectif est de permettre au par…

The prognosis of patients having received optimal therapy for nonvariceal upper gastrointestinal bleeding might be worse in daily practice than in randomized clinical trials.

International audience; BACKGROUND: Combination of endoscopic haemostatic and high-dose intravenous proton-pump inhibitors is considered to be the standard care for patients with acute peptic ulcer bleeding. AIM: This study assessed predictive factors of rebleeding and death in unselected patients presented to our hospital. METHODS: Consecutive patients with nonmalignant bleeding ulcers and stigmata of recent haemorrhage who received optimal treatment, between 22 August 2003 and 15 October 2007, were studied retrospectively. RESULTS: Among 140 included patients, 45 (32%) rebled and 30 received another haemostatic endoscopy, which was successful in 20 cases. In multivariate analysis, the onl…

Adrb3 adrenergic receptor is a key regulator of human myometrial apoptosis and inflammation during chorioamnionitis1

The pathophysiology underlying preterm labor triggered by inflammatory conditions such as chorioamnionitis remains largely unclear. It has already been suggested that beta-3 adrenergic (ADRB3) agonists might be of interest in the pharmacological management of preterm labor. Although there is evidence implicating ADRB receptors in the control of inflammation, there are minimal data relating specifically to ADRB3. To explore the cellular consequences of chorioamnionitis and detect apoptosis, we first performed immunostaining and Western blot experiments on human myometrial samples obtained from women with confirmed chorioamnionitis. We then developed an in vitro model of chorioamnionitis by i…