Publications of Jean DEFRAIGNE
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See detailCompared Phenolic Compound Contents of 22 Commercial Fruit and Vegetable Juices: Relationship to Ex-Vivo Vascular Reactivity and Potential In Vivo Projection
Matute Matute, Alexis Fernando ULiege; Tabart, Jessica ULiege; CHERAMY-BIEN, Jean-Paul ULiege et al

in Antioxidants (2020), 9(2), 92

The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were ... [more ▼]

The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were used to explore whether the total polyphenol content and/or individual phenolic compound contents of 22 commercial vegetable (n = 3) and fruit juices [(citrus (n = 5), berries (n = 10), apple (n = 2), pineapple (n = 2)] might be associated with vascular tone. Red juices (particularly blackcurrant) and lemon juice caused the most marked vasorelaxation, its amplitude being endothelium dependent or not according to the volume ratio of juice to initial OB solution Vjuice/VOBS). At volume ratios 5% and 10%, both the juice and OB total polyphenol for all juices and total anthocyanin contents for berry juices significantly correlated with aorta vasorelaxation intensity. This was not the case for total or individual flavonols (except kaempferol) or for total or individual flavanols (except epigallocatechin gallate). If one relates our measured concentrations of individual phenolic compounds in OB to what is known about their physiological concentrations, and given our evidenced correlations between compound concentrations and vasorelaxation intensity, kaempferol, epigallocatechin gallate and peonidin-3-O-glucoside seem to emerge as the interesting phenolic compounds likely to be responsible for the potent vasorelaxation observed with fruit juices, and more particularly blackcurrant ones. Clinical investigation is required, however, to confirm our observations. [less ▲]

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See detailLa transplantation cardiaque : indications actuelles et resultats de l'experience liegeoise.
BRULS, Samuel ULiege; Tchana-Sato, Vincent ULiege; LAVIGNE, Jean-Paul ULiege et al

in Revue medicale de Liege (2020), 75(1), 29-36

Heart transplantation remains undoubtedly the most effective treatment for end-stage heart failure, whatever its cause. Last decade has witnessed significant improvements in terms of morbidity and ... [more ▼]

Heart transplantation remains undoubtedly the most effective treatment for end-stage heart failure, whatever its cause. Last decade has witnessed significant improvements in terms of morbidity and mortality following heart transplant. The 5-year survival rate is now beyond 70 %. However, the shortage of potential donors limits its use and requires strict criteria before listing a candidate for heart transplantation. Herein, we present a review of current indications and results of the heart transplantation program at the University hospital of Liege. [less ▲]

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See detailMechanical strain induces a pro-fibrotic phenotype in human mitral valvular interstitial cells through RhoC/ROCK/MRTF-A and Erk1/2 signaling pathways
Blomme, Benoit ULiege; Deroanne, Christophe ULiege; Hulin, Alexia ULiege et al

in Journal of Molecular and Cellular Cardiology (2019), 135

The mitral valve is a complex multilayered structure populated by fibroblast-like cells, valvular interstitial cells (VIC) which are embedded in an extracellular matrix (ECM) scaffold and are submitted to ... [more ▼]

The mitral valve is a complex multilayered structure populated by fibroblast-like cells, valvular interstitial cells (VIC) which are embedded in an extracellular matrix (ECM) scaffold and are submitted to the mechanical deformations affecting valve at each heartbeat, for an average of 40 million times per year. Myxomatous mitral valve (MMV) is the most frequent heart valve disease characterized by disruption of several valvular structures due to alterations of their ECM preventing the complete closure of the valve resulting in symptoms of prolapse and regurgitation. VIC and their ECM exhibit reciprocal dynamic processes between the mechanical signals issued from the ECM and the modulation of VIC phenotype responsible for ECM homeostasis of the valve. Abnormal perception and responsiveness of VIC to mechanical stress may induce an inappropriate adaptative remodeling of the valve progressively leading to MMV. To investigate the response of human VIC to mechanical strain and identify the molecular mechanisms of mechano-transduction in these cells, a cyclic equibiaxial elongation of 14% at the cardiac frequency of 1.16 Hz was applied to VIC by using a Flexercell-4000 T™ apparatus for increasing time (from 1 h to 8 h). We showed that cyclic stretch induces an early (1 h) and transient over-expression of TGFβ2 and αSMA. CTGF, a profibrotic growth factor promoting the synthesis of ECM components, was strongly induced after 1 and 2 h of stretching and still upregulated at 8 h. The mechanical stress-induced CTGF up-regulation was dependent on RhoC, but not RhoA, as demonstrated by siRNA-mediated silencing approaches, and further supported by evidencing RhoC activation upon cell stretching and suppression of cell response by pharmacological inhibition of the effector ROCK1/2. It was also dependent on the MEK/Erk1/2 pathway which was activated by mechanical stress independently of RhoC and ROCK. Finally, mechanical stretching induced the nuclear translocation of myocardin related transcription factor-A (MRTF-A) which forms a transcriptional complex with SRF to promote the expression of target genes, notably CTGF. Treatment of stretched cultures with inhibitors of the identified pathways (ROCK1/2, MEK/Erk1/2, MRTF-A translocation) blocked CTGF overexpression and abrogated the increased MRTF-A nuclear translocation. CTGF is up-regulated in many pathological processes involving mechanically challenged organs, promotes ECM accumulation and is considered as a hallmark of fibrotic diseases. Pharmacological targeting of MRTF-A by newly developed inhibitors may represent a relevant therapy for MMV. © 2019 [less ▲]

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See detailAnalyse détaillée de la seconde version de l’avant-projet de Code du bien-être animal wallon. Lecture commentée au 21/03/2018 du Chapitre 8 (Expérimentation animale)
Drion, Pierre ULiege; Corhay, Albert ULiege; Haubruge, Eric ULiege et al

Report (2018)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984 et ses modifications, aujourd’hui, le projet de code pour la Région wallonne). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la Directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

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See detailAfterload burden on the right ventricle is enhanced when ARDS is associated with hypercapnic acidosis.
MORIMONT, Philippe ULiege; Habran, Simon ULiege; Desaive, Thomas ULiege et al

in Annals of Intensive Care (2018, February 05), 8(1),

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See detailLes urgences cardiaques et vasculaires : du diagnostic au traitement.
Scheen, André ULiege; Lancellotti, Patrizio ULiege; Defraigne, Jean-Olivier ULiege et al

in Revue Médicale de Liège (2018), 73(5-6), 221-223

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See detailWhat we need to know about lipid-associated injury in case of renal ischemia/reperfusion.
ERPICUM, Pauline ULiege; Rowart, Pascal ULiege; Defraigne, Jean-Olivier ULiege et al

in American Journal of Physiology. Renal Physiology (2018)

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion ... [more ▼]

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch towards anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting to a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI. [less ▲]

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See detailL'ischemie mesenterique aigue.
KERZMANN, Arnaud ULiege; HAUMANN, Alexandre ULiege; BOESMANS, Evelyne ULiege et al

in Revue Médicale de Liège (2018), 73(5-6), 300-303

Acute mesenteric ischemia is a real life-threatening emergency. Mode of presentation is severe abdominal pain with sudden onset. The etiology is most of the time embolus coming from the heart or ... [more ▼]

Acute mesenteric ischemia is a real life-threatening emergency. Mode of presentation is severe abdominal pain with sudden onset. The etiology is most of the time embolus coming from the heart or thrombosis of atherosclerotic vessel wall concerning the superior mesenteric artery. The best investigation is computed tomography with intravenous contrast media injection. Treatment consists of revascularization by open surgery or endovascular approach. Bowel resection may be necessary, as well as delayed second look surgery. This paper aims to review etiologies and therapeutics options for acute mesenteric ischemia. [less ▲]

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See detailPolyphenol content and antioxidant capacity in various commercial juices
Matute Matute, Alexis Fernando ULiege; Tabart, Jessica ULiege; CHERAMY-BIEN, Jean-Paul ULiege et al

Poster (2016, November 16)

Antioxidants are enzymes, non-enzymatic proteins, minerals micronutrients, vitamins, phenolic compounds, pigments and others. Polyphenols have the ability to reduce or prevent damage caused by free ... [more ▼]

Antioxidants are enzymes, non-enzymatic proteins, minerals micronutrients, vitamins, phenolic compounds, pigments and others. Polyphenols have the ability to reduce or prevent damage caused by free radicals promoting positive effects on human health due to their antioxidant capacity. In this study we evaluated the content of polyphenols from several commercial biological (n = 6) and conventional juices (n = 6 ) (orange, blackcurrant, apple, grapes, tomato, carrot, pomegranate, lemon, grapefruit juices) and we determined the antioxidant effect by inhibition of the superoxide anion production measured by chemiluminescence technology. Conventional juices (orange, apple, tomato, pomegranate, lemon, grapefruit juices) showed more total polyphenolics (+ 32%), more flavan-3-ols (+ 67%) and more flavonols (+ 42%) than the same biological juices. The presence of anthocyanins was reported in juices made with blackcurrant, pomegranate and grapes only, with values above 50 µg/mL, regardless of their nature. Surprisingly, chemiluminescence results showed an inhibition in superoxide anion production by 51% for biological juices vs 23% in conventional ones. The correlation between total polyphenol content and antioxidant capacity of all the juices was r = 0.83 (r2 = 0.7). The fact that there is less polyphenols and higher antioxidant activity in bio juices could be related to the concentration and the type of polyphenol present. [less ▲]

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See detailNuclear Magnetic Resonance Metabolomic Profiling of Mouse Kidney, Urine and Serum Following Renal Ischemia/Reperfusion Injury.
Jouret, François ULiege; Leenders, Justine ULiege; Defraigne, Jean-Olivier ULiege et al

in PLoS ONE (2016), 11(9), 1-14

Abstract BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in ... [more ▼]

Abstract BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in (patho)physiological changes of integrated living systems. Here, we performed 1H-Nuclear Magnetic Resonance metabolomics using urine, serum and kidney samples from a mouse model of renal I/R. METHODS: Renal 30-min ischemia was induced in 12-week-old C57BL/6J male mice by bilaterally clamping vascular pedicles, and was followed by 6, 24 or 48-hour reperfusion (n = 12/group). Sham-operated mice were used as controls. Statistical discriminant analyses, i.e. principal component analysis and orthogonal projections to latent structures (OPLS-DA), were performed on urine, serum and kidney lysates at each time-point. Multivariate receiver operating characteristic (ROC) curves were drawn, and sensitivity and specificity were calculated from ROC confusion matrix (with averaged class probabilities across 100 cross-validations). RESULTS: Urine OPLS-DA analysis showed a net separation between I/R and sham groups, with significant variations in levels of taurine, di- and tri-methylamine, creatine and lactate. Such changes were observed as early as 6 hours post reperfusion. Major metabolome modifications occurred at 24h post reperfusion. At this time-point, correlation coefficients between urine spectra and conventional AKI biomarkers, i.e. serum creatinine and urea levels, reached 0.94 and 0.95, respectively. The area under ROC curve at 6h, 24h and 48h post surgery were 0.73, 0.98 and 0.97, respectively. Similar discriminations were found in kidney samples, with changes in levels of lactate, fatty acids, choline and taurine. By contrast, serum OPLS-DA analysis could not discriminate sham-operated from I/R-exposed animals. CONCLUSIONS: Our study demonstrates that renal I/R in mouse causes early and sustained metabolomic changes in urine and kidney composition. The most implicated pathways at 6h and 24h post reperfusion include gluconeogenesis, taurine and hypotaurine metabolism, whereas protein biosynthesis, glycolysis, and galactose and arginine metabolism are key at 48h post reperfusion. [less ▲]

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See detailDu processus aux soins intégrés: Expérience de gestion de projet bottom-up
ERPICUM, Marie ULiege; BASSLEER, Bernard ULiege; DEFRAIGNE, Jean ULiege et al

in Gestions Hospitalieres (2016), 558(Août/septembre 2016),

Le service de chirurgie cardiaque du CHU de Liège a soutenu des recherches visant à développer un programme d’épargne sanguine, enjeu actuel de taille dans ce secteur des soins de santé. Ce projet a ... [more ▼]

Le service de chirurgie cardiaque du CHU de Liège a soutenu des recherches visant à développer un programme d’épargne sanguine, enjeu actuel de taille dans ce secteur des soins de santé. Ce projet a évolué vers la création d’un itinéraire clinique chirurgical cardiaque et d’un modèle institutionnel pour le développement d’autres itinéraires cliniques. Une évolution qui permet de déterminer les missions spécifiques de l’institution et ses objectifs stratégiques, et de s’associer aux projets nationaux. L’adhésion multidisciplinaire, soutenue par un leadership médical et infirmier, ainsi que la reconnaissance institutionnelle sont les déterminants de la pérennité de cette démarche bottom-up. [less ▲]

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See detailRenal ischemia/reperfusion decreases the expression of DPP-4
Rowart, Pascal ULiege; ERPICUM, Pauline ULiege; Defraigne, Jean-Olivier ULiege et al

Conference (2015, April 24)

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See detailMolding thrombus of an ECMO cannula floating in the right atrium.
MORIMONT, Philippe ULiege; LAMBERMONT, Bernard ULiege; GARSPARD, Valérie ULiege et al

in Intensive Care Medicine (2015), 41(11), 1965-1966

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See detailEtude GEROX : Evaluation du statut de stress oxydant
CHRISTELBACH, SOPHIE; RICOUR, Céline ULiege; Dardenne, Nadia ULiege et al

Poster (2015, March)

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See detailVeno-venous extracorporeal CO2 removal improves pulmonary hemodynamics in a porcine ARDS model
MORIMONT, Philippe ULiege; GUIOT, Julien ULiege; Desaive, Thomas ULiege et al

in Acta Anaesthesiologica Scandinavica (2015), 59(4), 448-456

BACKGROUND: Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ... [more ▼]

BACKGROUND: Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno-venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function. METHODS: This study was performed on an experimental model of ARDS obtained in eight anaesthetized pigs connected to a volume-cycled ventilator. A micromanometer-tipped catheter was inserted into the main pulmonary artery and an admittance micromanometer-tipped catheter was inserted into the right ventricle. RV-arterial coupling was derived from RV pressure-volume loops. ARDS was obtained by repeated bronchoalveolar lavage. Protective ventilation was then achieved, and the pigs were connected to a pump-driven extracorporeal membrane oxygenator (PALP, Maquet, Germany) in order to achieve CO2 removal. RESULTS: ARDS induced severe hypercapnic acidosis. Systolic pulmonary artery pressure significantly increased from 29.6 ± 1.8 to 43.9 ± 2.0 mmHg (P < 0.001). After the PALP was started, acidosis was corrected and normocarbia was maintained despite protective ventilation. Pulmonary artery pressure significantly decreased to 31.6 ± 3.2 mmHg (P < 0.001) and RV-arterial coupling significantly improved (RV-arterial coupling index = 1.03 ± 0.33 vs. 0.55 ± 0.41, P < 0.05). CONCLUSION: Veno-venous CO2 removal therapy enabled protective ventilation while maintaining normocarbia during ARDS. CO2 removal decreased pulmonary hypertension and improved RV function. This technique may be an effective lung- and RV-protective adjunct to mechanical ventilation. [less ▲]

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See detailActivation of the calcium-sensing receptor before renal ischemia/reperfusion exacerbates kidney injury
WEEKERS, Laurent ULiege; De Tullio, Pascal ULiege; BOVY, Christophe ULiege et al

in American Journal of Translational Research (2015), 7(1), 128-138

Activation of the calcium-sensing receptor (CaSR) by ischemia/reperfusion (I/R) favours apoptosis in cardiomyocytes, hepatocytes and neurons. Its role in renal I/R is unknown. We investigated the impact ... [more ▼]

Activation of the calcium-sensing receptor (CaSR) by ischemia/reperfusion (I/R) favours apoptosis in cardiomyocytes, hepatocytes and neurons. Its role in renal I/R is unknown. We investigated the impact of pharmacological preactivation of the CaSR on kidney structure and function in a murine model of bilateral renal 30-min ischemia and 48-hour reperfusion, and in a 6-year cohort of kidney transplant recipients (KTR). C57BL/6J mice were administered daily with CaSR agonist, R-568, or with vehicle for 48 hours. Evaluation of serum urea and creatinine levels, renal histology and urine metabolome by nuclear magnetic resonance showed that R-568 was not nephrotoxic per se. Following I/R, serum urea and creatinine levels increased higher in R-568-treated animals than in controls. Jablonski’s score was significantly greater in R-568-treated kidneys, which showed a higher rate of cell proliferation and apoptosis in comparison to controls. Next, we retrospectively identified 36 patients (10.7% of our cohort) who were treated by CaSR agonist, cinacalcet, at the time of kidney transplantation (KTx). After matching these to 61 KTR upon type of donor, cold ischemic time, residual diuresis, and donor age, we observed that delayed graft function, i.e. need for dialysis in the first week after KTx, occurred in 42 and 23% of cinacalcet-treated and control groups, respectively (p≤0.05). These data suggest that pharmacological preactivation of the CaSR before renal I/R exacerbates kidney injury. [less ▲]

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See detailCervical artery dissections and type A aortic dissection in a family with a novel missense COL3A1 mutation of vascular type Ehlers-Danlos syndrome.
Makrygiannis, Georgios ULiege; Loeys, Bart; Defraigne, Jean-Olivier ULiege et al

in European Journal of Medical Genetics (2015)

Cervical artery dissection (CeAD) is a rare condition. One of the causes is the vascular type of Ehlers-Danlos syndrome (vEDS). A novel missense mutation in COL3A1 was found in a young patient with CeAD ... [more ▼]

Cervical artery dissection (CeAD) is a rare condition. One of the causes is the vascular type of Ehlers-Danlos syndrome (vEDS). A novel missense mutation in COL3A1 was found in a young patient with CeAD as the single manifestation of vEDS. This is a heterozygous c.953G>A mutation in exon 14, disrupting the normal Gly-X-Y repeats of type III procollagen, by converting glycine to aspartic acid. [less ▲]

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