15 research outputs found
Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study
BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12âgâdl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (â„week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] gâdl-1 for neonates in week 1, 9.6 [7.7 to 10.4] gâdl-1 in week 2 and 8.0 [7.3 to 9.0] gâdl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] mlâkg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] gâdl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348
Polyphenolic-protein-polysaccharide ternary conjugates from Cystoseira barbata Tunisian seaweed as potential biopreservatives: Chemical, antioxidant and antimicrobial properties
The present study investigated the antioxidant and antimicrobial activities of naturally occurring Cystoseira barbata seaweed glyco-conjugates (CBGs), with a view to developing safer food preservatives. CBGs were successfully isolated, then chemically and structurally characterized. CBGs contained a high amount of polysaccharides (49.76%) that consisted mainly of neutral sugars (47.67%) and uronic acids (2.09%). The carbohydrate fraction was sulfated (13.81%) and conjugated with proteins (9.86%) and phenolic compounds (4.98%). Infrared spectroscopy of CBGs showed interactions between polyphenols, proteins and polysaccharides, which were characterized by α-type glycosidic bond and sulfate groups in the axial position of sugar residues. Neutral sugars analysis of CBGs by GCâMS revealed that conjugated polysaccharides were mainly composed of galactose (34.02%), fucose (26.25%) and mannitol (21.25%) with few amounts of other sugars such as glucose (5.78%), rhamnose (4.9%), xylose (3.22%) and mannose (2.22%). Analysis of the amino acid composition of CBGs showed a high level of essential amino acids (40.36%), in which threonine was the most relevant (10.28%). LC-QTOF-MS analysis of the phenolic fraction of CBGs showed a variety of phenolic compounds including flavonoids, phlorotannins and anthraquinone glycosides. CBGs exhibited potent antioxidant activities including radical scavenging activity, chelating ability and reducing power, and displayed noticeable antibacterial and antifungal activities, which may open the way to the development of a natural biopreservation strategy based on algae
Safer and healthier reduced nitrites turkey meat sausages using lyophilized Cystoseira barbata seaweed extract
The Angiogenic Balance and Its Implications in Cancer and Cardiovascular Diseases: An Overview
Angiogenesis is the process of developing new blood vessels from pre-existing ones. This review summarizes the main features of physiological and pathological angiogenesis and those of angiogenesis activation and inhibition. In healthy adults, angiogenesis is absent apart from its involvement in female reproductive functions and tissue regeneration. Angiogenesis is a complex process regulated by the action of specific activators and inhibitors. In certain diseases, modulating the angiogenic balance can be a therapeutic route, either by inhibiting angiogenesis (for example in the case of tumor angiogenesis), or by trying to activate the process of new blood vessels formation, which is the goal in case of cardiac or peripheral ischemia
alpha v integrin processing interferes with the cross-talk between alpha v beta 5/beta 6 and alpha 2 beta 1 integrins
International audienceBackground information. Previous studies have reported that cross-talk between integrins may be an important regulator of integrin-ligand binding and subsequent signalling events that control a variety of cell functions in many tissues. We previously demonstrated that alpha v beta 5/beta 6 integrin represses alpha 2 beta 1-dependent cell migration. The alpha v subunits undergo an endoproteolytic cleavage by protein convertases, whose role in tumoral invasion has remained controversial. Results. Inhibition of convertases by the convertase inhibitor alpha 1-PDX (alpha 1-antitrypsin Portland variant), leading to the cell-surface expression of an uncleaved form of the av integrin, stimulated cell migration toward type I collagen. Under convertase inhibition, alpha 2 beta 1 engagement led to enhanced phosphorylation of both FAK (focal adhesion kinase) and MAPK (mitogen-activated protein kinase). This outside-in signalling stimulation was associated with increased levels of activated integrin located in larger than usual focal-adhesion structures and a cell migration that was independent of the PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) pathway. Conclusions. The increase in cell migration observed upon convertases inhibition appears to be due to the up-regulation of beta 1 integrins and to their location in larger focal-adhesion structures. The endoproteolytic cleavage of av subunits is necessary for alpha v beta 5/beta 6 integrin to control alpha 2 beta 1 function and could thus play an essential role in colon cancer cell migration
alpha v beta 5/beta 6 integrin suppression leads to a stimulation of alpha 2 beta 1 dependent cell migration resistant to PI3K/Akt inhibition
International audienceCrosstalk between integrins is involved in the regulation of various cell functions including cell migration. Here we identify the interplay between the integrins αvÎČ5/ÎČ6 and α2ÎČ1 during cell migration toward type I collagen. Human colon cancer cell lines HT29-D4 and SW480 were used as cell models. To improve our understanding of the consequences of αvÎČ5/ÎČ6 function on α2ÎČ1, we decreased the expression of αv integrins by either siRNA or lysosomal targeting strategies or inhibited their function using, as antagonists, blocking antibodies or disintegrins. In all cases, we observed a greatly enhanced α2ÎČ1 integrin-dependent cell migration associated with focal adhesion rearrangements and increased outside-in signaling as demonstrated by elevated phosphorylation of focal adhesion kinase and MAPKinase (ERK1 and ERK2). The αvÎČ5/ÎČ6-dependent limitation of α2ÎČ1 function could be overridden by TS2/16, an activating anti-ÎČ1 antibody. Interestingly, compared to control cells, the pharmacological inhibition of PI3Kinase or the siRNA-mediated knockdown of AKT had little effect on the high α2ÎČ1-mediated cell migration observed in the absence of αv integrins or following activation of α2ÎČ1 integrins by the TS2/16. These results suggest that integrins αvÎČ5/ÎČ6 repress α2ÎČ1 possibly by interfering with their activation process and thereby modify the cell signaling regulation of α2ÎČ1-mediated migration
Akt targeting as a strategy to boost chemotherapy efficacy in non-small cell lung cancer through metabolism suppression.
International audienceMetabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting Akt activity could improve therapy of non-small cell lung cancer (NSCLC) that represents more than 80% of all lung cancer cases. First, we demonstrated that Akt inhibitors interacted synergistically with Microtubule-Targeting Agents (MTAs) and specifically in cancer cell lines, including those resistant to chemotherapy agents and anti-EGFR targeted therapies. In vivo, we further revealed that the chronic administration of low-doses of paclitaxel - i.e. metronomic scheduling - and the anti-Akt perifosine was the most efficient and the best tolerated treatment against NSCLC. Regarding drug mechanism of action, perifosine potentiated the pro-apoptotic effects of paclitaxel, independently of cell cycle arrest, and combining paclitaxel/perifosine resulted in a sustained suppression of glycolytic and mitochondrial metabolism. This study points out that targeting cancer cell bioenergetics may represent a novel therapeutic avenue in NSCLC, and provides a strong foundation for future clinical trials of metronomic MTAs combined with Akt inhibitors