Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined “BNP-cTnI” levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers. We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Participation to the study of the adenosinergic system role in cardiovascular pathology

L'adénosine est un nucléotide purinergique ubiquitaire qui exerce plusieurs fonctions dans l'organisme, notamment au sein du tissu cardiovasculaire, via ses 4 récepteurs RCPGs: A1, A2a, A2B, A3. Le système adénosinergique est donc particulièrement impliqué dans la pathologie cardiovasculaire et en particulier dans la maladie coronarienne et dans la fibrillation auriculaire.Dans la maladie coronarienne, le rôle du récepteur A2a est crucial puisqu'il participe au contrôle du flux coronaire. Nous avons comparé le niveau d’expression de ce récepteur dans les cellules mononuclées circulantes et dans des fragments d’artères coronaires prélevés chez des patients atteints de coronaropathie. L’expression du récepteur A2a dans les PBMCs est corrélée à celle mesurée dans les artères coronaires. Ces résultats indiquent que le récepteur A2a exprimé par les PBMCs a un comportement similaire à celui de son homologue in situ.L’adénosine affecte également le rythme cardiaque. Nous avons donc étudié son implication, via les récepteurs A1 et A2a, dans la fibrillation auriculaire. Nous avons observé une élévation très importante de l’adénosine dans la cavité auriculaire au cours de l’épisode de fibrillation auriculaire, et cette augmentation de l’adénosinémie pourrait participer à la permanence de la fibrillation.Dans une troisième partie nous avons évalué la corrélation entre les valeurs de l’ionogramme sanguin et celles de l’ionogramme sudoral et nous avons observé une corrélation entre la kaliémie et le potassium sudoral. Cela pourrait permettre de surveiller de manière continue etnon invasive les dyskaliémies, actrices des troubles du rythme.The adenosine is an ubiquitous purinergic nucleotide which performs several functions in the body, in particular within the cardiovascular system, via his 4 receptors GPCRs: A1, A2a, A2B, A3. Thus the adenosinergic system is particularly involved in the cardiovascular pathology and in particular in the coronary disease and in the atrial fibrillation.In the coronary disease, the role of the A2a receptor is crucial because it participates in the control of the coronary flow. We compared the level of expression of this receptor in PBçCs and in fragments of coronary arteries taken from patients with coronaropathie. The expression of the A2a receptor in the PBMCs is correlated with that measured in the coronary arteries. These results indicate that the A2a receptor expressed by the PBMCs has a behavior similar to that of his in situ counterpart.The adenosine also modulates the heart rhythm. We thus studied her implication, via the A1 and A2a receptor, in the atrial fibrillation. We observed a very important rise of the adenosine in the left atrium during the episode of fibrillation, and we suggest that this increase in peripheral adenosine concentration could participate in the durability of the fibrillation.In the third part we estimated the correlation between the values of the blood ionogramme and those of the sweat ionogramme and we observed a correlation between the bllod concentration of potassium and the sweatpotassium. It could allow monitoring in a continuous and non-invasive way changes in blood potassium concentration which has a major role in cardiac rhytm diseases

Extracellular vesicles with ubiquitinated adenosine A 2A receptor in plasma of patients with coronary artery disease

International audienceINTRODUC TI ON Extracellular vesicles (EV) such as exosomes and microvesicles are bi-lipid membranous vesicles with endocytic origin that are released by many cell types including immune, endothelial and mesenchymal stem cells, erythrocytes and platelets. 1 EV participate in intercellular communication by carrying and delivering cargo including proteins, lipids, miRNA and mRNA specific to the type of cell from which they originate. 2 EV are key mediators of a process now thought to be a form of intercellular signalling that impacts the physiology of cells, tissues and organs. 3 EV are released constitutively or after stimulation and taken up by other cells via membrane fusion or ligand-receptor interactions. 4 Due to their ability to trap their cargo and circulate freely in body fluids, EV are natural sources of non-invasive diagnostic and prognostic biomarkers that may also be used as vehicles of targeted therapy for tumour progression, neurodegeneration, autoimmune Abstract Extracellular vesicles (EV) can transfer cellular molecules for specific intercellular communication with potential relevance in pathological conditions. We searched for the presence in plasma from coronary artery disease (CAD) patients of EV containing the adenosine A 2A receptor (A 2A R), a signalling receptor associated with myocardial ischaemia and whose expression is related to homocysteine (HCy) metabolism. Using protein organic solvent precipitation for plasma EV preparation and Western blotting for protein identification, we found that plasma from CAD patients contained various amounts of EV with ubiquitin bound to A 2A R. Interestingly, the presence of ubiquitinated A 2A R in EV from patients was dependent on hyperhomocysteinemia, the amount being inversely proportional to A 2A R expression in peripheral mononu-clear cells in patients with the highest levels of HCy. CEM, a human T cell line, was also found to released EV containing various amounts of ubiquitinated A 2A R in stimulated conditions depending on the hypoxic status and HCy level of culture medium. Together, these data show that ubiquitinated A 2A R-containing EV circulate in the plasma of CAD patients and that this presence is related to hyperhomocysteinemia. A 2A R in plasma EV could be a useful tool for diagnosis and a promising drug for the treatment of CAD

Hypoxic preconditioning in renal ischaemia–reperfusion injury: a review in pre-clinical models

International audienceAbstract Ischaemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and chronic kidney disease, which consists of cellular damage and renal dysfunction. AKI is a major complication that is of particular concern after cardiac surgery and to a lesser degree following organ transplantation in the immediate post-transplantation period, leading to delayed graft function. Because effective therapies are still unavailable, several recent studies have explored the potential benefit of hypoxic preconditioning (HPC) on IRI. HPC refers to the acquisition of increased organ tolerance to subsequent ischaemic or severe hypoxic injury, and experimental evidences suggest a potential benefit of HPC. There are three experimental forms of HPC, and, for better clarity, we named them as follows: physical HPC, HPC via treated-cell administration and stabilised hypoxia-inducible factor (HIF)-1α HPC, or mimicked HPC. The purpose of this review is to present the latest developments in the literature on HPC in the context of renal IRI in pre-clinical models. The data we compiled suggest that preconditional activation of hypoxia pathways protects against renal IRI, suggesting that HPC could be used in the treatment of renal IRI in transplantation

Nutritional benefits of the Black Soldier Fly reared on different biowaste.

Since there is more than 20 million tons of biowaste produced in France every year, the exploratory project FLY4WASTE aims at assessing the benefits and risks of the insect-based bioconversion of these biowaste by the Black Soldier Fly, Hermetia illucens, in a context of circular bioeconomy. Indeed, the Black Soldier Fly Larvae (BSFL) can convert a wide variety of biowaste and be used as a new feed source. BSFL are rich in proteins and lipids and they can bioaccumulate different micronutrients, i.e. vitamins and minerals, as well as some phytochemicals such as carotenoids, depending on thesubstrate they are reared on. BSFL are increasingly used to feed animals because they are a more sustainable source of proteins than soya for example, and can be an alternative that provides proteins of good quality as well. Not all substrates on which BSFL can grow are approved for rearing larvae for animal feed for precautionary measures. Indeed, some chemical or microbiological contaminants might be present in these substrates and might be transmitted in the food chain. From a sustainability perspective, it would be preferable to use substrates that cannot be used to feed farm animals to feed BSFLs. Therefore we are going to study the organic waste from school canteens and from large and medium-sized supermarkets that are not yet authorized by the EU legislation and those already authorized: the agricultural by-products. The objective of the first task (C2VN, Marseille) is to measure the main macronutrients of interest in the larvae (proteins and lipids) as well as their content in fatsoluble micronutrients (carotenoids and vitamins A, D and E), to assess the ability of these substrates to improve the nutritional quality of the larvae. BSFL were reared on different biowaste at Avignon by the company BioMiMetiC. Lipids will be quantified following a modified Bligh& Dyer method and proteins using the Bradford method. Fat-soluble vitamins A, D and E and carotenoids will be quantified using a double extraction with hexane and HPLC quantification. Results will be presented during the congress. The second part of the project will focus on the identification and quantification of the potential chemical contaminants that might bioaccumulate in the larvae (INRAE, Clermont-Ferrand)

Impact of pulses, starches and meat on vitamin D and K postprandial responses in mice

International audienceIn vitro experiments showed that i) phytates, tannins and saponins from pulses can alter vitamin D and K bioavailability and ii) meat decreased vitamin D bioaccessibility by impairing its stability during digestion. We aimed to confirm these results in vivo by force-feeding mice with emulsions containing either potatoes or semolina or chickpeas or meat. Vitamin D and K plasma responses decreased after a gavage with chickpeas or meat compared with potatoes (− 62 % and − 67 %, respectively for vitamin D, − 40 % and − 64 %, respectively for vitamin K; p < 0.05). Vitamin D and K intestinal contents were also reduced in mice force-fed with chickpeas or meat compared with potatoes (from − 64 to − 83 % and from − 76 to − 84 %, respectively for vitamin D and from − 7 to − 59 % and from − 7 to − 90 %, respectively for vitamin K; p < 0.05). The results confirm that chickpea and meat compounds can decrease vitamin D and K bioavailability

Correlation between low adenosine A2A receptor expression and hypercholesterolemia: A new component of the cardiovascular risk?

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Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias

International audienceAbetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (−57.0 ± 2.6% to −83.9 ± 1.6%) and cholesterol (−35.3 ± 4.4% to −60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (−41.5 ± 3.7% to −97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism

Corrigendum to “A case of false positive cardiac troponin I in CANOMAD syndrome” [Int. J. Cardiol. 222 (2016) 359–360]

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