steroid hormones in muscles, and into muscle pathophysiology.

Conclusion: Candesartan decreases the vulnerability to

For instance, we have demonstrated that androgens and pressure-induced ulceration and restores skin neurovascular
glucocorticoids, via their receptor in myofibers, control limb functions in mice with STZ-induced established diabetes.
muscle strength but not mass, and exert both anti-anabolic and
catabolic activities in skeletal muscles, respectively. In addition, CO-01-002:
we have shown that the transcriptional coregulator PGC-1
controls mitochondrial function and anti-oxidant defense in B-TYPE NT-PROBNP AS A MARKER FOR
skeletal muscles, that muscle fiber type switching towards lower CONTRAST INDUCED NEPHROPATHY IN
oxidative capacity promotes obesity and diabetes, and that PATIENTS WITH PRIMARY
increased mitochondrial uncoupling in myofibers protects mice PERCUTANEOUS CORONARY
from decreased muscle oxidative capacity induced by INTERVENTION FOR ST SEGMENT
sedentariness and delays the development of type 2 diabetes.
ELEVATION MYOCARDIAL INFARCTION
Samuel GOUSSOT, Shabab DARBANI, Karim STAMBOUL,
Thematic Sessions of the SFP Philippe BRUNEL, Damien BRUNET, Claude TOUZERY,
Maud MAZA, Yves COTTIN, Marianne ZELLER
(Oral presentations) Service de Cardiologie, Paris.
Introduction: Contrast induced nephropathy (CIN) after
Percutaneous Coronary Intervention (PCI) for ST segment
Cardiovascular system elevation myocardial infarction (STEMI) is frequent and
associated with worse prognosis. Improving risk stratification of
CO-01-001 such patients by early markers is needed. We aimed at assessing
ANGIOTENSIN RECEPTOR BLOCKADE the association between Nt-proBNP, as an integrated biomarker
for altered ventricular dysfunction and renal function, and the
RESTORES PRESSURE INDUCED- development of CIN.
VASODILATION AND PREVENTS SKIN Material and Methods: From the (RICO) survey, consecutive
PRESSURE ULCER FORMATION IN patients undergoing a PCI for a STEMI were included. Patients
DIABETIC MICE with cardiogenic shock or severe kidney disease were excluded.
Jean-Michel ACHARD1, James JAVELLAUD1, Flavien Serum creatinine (Cr) was measured at admission and 48h after
BESSAGUET2, Aurore DANIGO2, Claire DEMIOT2 PCI. CIN was defined as a rise in Cr >26.5µmol/L or > 50 %
1
EA3842, Faculté de Médecine et Pharmacie - Université de from baseline. Nt-proBNP was assessed on admission.
Limoges, 87025 Limoges Cedex, 2EA 6309, Faculté de Médecine Results: Among the 1243 patients included, CIN occurred in 130
et Pharmacie – Université de Limoges, 87025 Limoges Cedex, (10.4 %) patients. Patients who developed CIN had a 5 fold
France increase in Nt-proBNP levels when compared with patients
Introduction: Angiotensin II type 1 receptor (AT1R) blockers without CIN (1275 (435-4022) vs 247 (79-986) pg/mL,
have beneficial effects on neurovascular complications in p<0.001). Hospital mortality was markedly higher in patients
diabetes and in organ’s protection against ischemic episodes. The with CIN (6.9 % vs 1.1 %, p<0.001). By multivariate analysis,
present study examines whether the AT1R blocker candesartan Nt-proBNP levels remains strongly associated with the
(1) has beneficial effect on diabetes-induced alteration of occurrence of CIN even after adjustment for risk factors,
pressure-induced vasodilation (a cutaneous physiological treatments, clinical, and biological variables (OR(95%CI):
neurovascular mechanism delaying the occurrence of tissue 1.91(1.40-2.60), p<0.001).
ischemia), and (2) could be protective against skin pressure ulcer Conclusion: From this large contemporary prospective study,
formation. our work suggests that Nt-proBNP levels at admission could help
Material and Methods: Diabetes was induced in Swiss mice by to identify patients at risk of CIN beyond traditional risk factors.
a single intraperitoneal injection of streptozotocin (STZ, 200 mg
kg-1). After 6 weeks, control and STZ mice received either no CO-01-003:
treatment or candesartan (1 mg/kg-daily in drinking water) CORRELATION BETWEEN CARDIO-
during 2 weeks. At the end of treatment (8 weeks of diabetes PULMONARY EXERCISE TEST VARIABLES
duration), C-fiber mediated nociception threshold, endothelium-
dependent vasodilation, and pressure-induced vasodilation were AND HEALTH-RELATED QUALITY OF LIFE
assessed. Pressure ulcer was then induced by pinching the dorsal AMONG CHILDREN WITH CONGENITAL
skin between two magnetic plates for three hours. Skin ulcer area HEART DISEASES
development was assessed during three days, and histological Stefan MATECKI1, Caroline OVAERT2, Sophie
examination of the depth of the skin lesion was performed at day GUILLAUMONT , Marie-Christine PICOT4, Stéphane
3

three. MONIOTTE5, Pascal AMEDRO6, Raphael DORKA7, Pascal

Results: After 8 weeks of diabetes, the skin neurovascular AUQUIER8
1
functions (C-fiber nociception, endothelium-dependent CHU Montpellier, 2APHM Timone Marseille, 3Institut-St-
vasodilation and PIV) were markedly altered in STZ-treated Pierre, 4CHU Montpellier, 5Cliniques Saint-Luc-UCL, 6CHU
mice, but were fully restored by treatment with candesartan. Montpellier, 7CHU Montpellier, 8Faculté de Médecine
Whereas exposure of the skin to pressure induced large and deep Marseille.
necrotic lesions in diabetes mice, treatment with candersartan Introduction: VO2max correlates with health related quality of
restored their ability to resist to pressure-induced ulceration as life (QoL) in adults with heart failure. Cardio-pulmonary
efficiently as the control mice. exercise test (CPET) is recommended in the follow-up of adults

4
with congenital heart diseases (CHD). Few data is available as MITOCHONDRIAL GRADIENT IS
regards correlation between CPET and QoL among children with ASSOCIATED WITH INCREASED NITRIC
CHD.
Method: 201 CHD children aged from 8 to 18 performed a OXIDE PRODUCTION IN THE
CPET (treadmill n=96, cycle-ergometer n=105) with a severity SUBENDOCARDIUM
stratified into 4 groups. All children and parents filled out the Michel KINDO1, Sébastien GERELLI2, Jamal BOUITBIR3,
Kidscreen QoL questionnaire. TAM HOANG MINH4, Anne-Laure CHARLES4, Joffrey
Results: Physical well-being was correlated to VO2max for ZOLL4, François PIQUARD4, Bernard GENY4
1
parents reported QoL (r=0.43, p<0.0001) and children self- Service de Chirurgie Cardiovasculaire, Nouvel Hôpital Civil,
reported QoL (r=0.27, p<0.0001). Parents-reported QoL was CHRU de Strasbourg, 2Service de Chirurgie Cardiovasculaire,
correlated to AT (r=0.33, p<0.0001), VD/VTmax (r=-0.30, Nouvel Hôpital Civil, CHRU de Strasbourg, 3Clinical
p<0.0001) for physical well-being and to VO2max (r=0.21, Pharmacology & Toxicology and Department of Biomedicine,
p=0.004) for psychological well-being. Self reported QoL was University Hospital Basel, Switzerland, 4Service de Chirurgie
correlated to oxygen uptake efficiency slope (r=-0.26, p=0.017), Cardiovasculaire, Nouvel Hôpital Civil, CHRU de Strasbourg,
VE/VCO2 slope (r=0.22, p=0.037) for school environment. Strasbourg, France, EA3072, Mitochondrie, Stress Oxydant et
Strongest correlations were observed in the treadmill group, Protection Musculaire, Faculté de Médecine, FMTS, Université
especially between VO2 max and physical well-being for parents de Strasbourg, France
(r=0.57, p<0.0001) and self (r=0.36, p=0.0005)-reported QoL. Introduction: Left ventricle (LV) transmural gradient in
Conclusion: VO2max and ventilatory response to exercise mitochondrial respiration has been recently reported previously
correlate with self- and parents-reported QoL among CHD but the mechanisms involved remains to be determined. Nitric
children. If QoL and CPET are clinical trial outcomes in CHD oxide (NO) synthase expression in the heart has spatial
children, we suggest to use parents-related QoL scores and heterogeneity and we investigated whether a LV transmural NO
treadmill. gradient might be associated with mitochondrial function in rat
subendocardium (Endo) and subepicardium (Epi).
CO-01-004 Methods: Electron paramagnetic resonance (RPE) determined
NO production, mitochondrial respiration rates using different
DISCOVERY AND CARDIOPROTECTIVE substrates, mitochondrial reactive oxygen species production
EFFECTS OF THE FIRST NON-PEPTIDE (H2O2), citrate synthase activity and superoxide anion were also
AGONISTS OF THE G PROTEIN-COUPLED assessed in both layers. Finally, maximal mitochondrial
PROKINETICIN RECEPTOR-1 respiratory rates (Vmax) were measured in presence of
Adeline GASSER, Simone BROGI, Kyoji URAYAMA, increasing concentration of MAHMA NONOate, a direct NO
Toshihide NISHI, Hitoshi KUROSE, Andrea TAFI, Canan donor.
NEBIGIL Results: NO production was 2-fold higher in the Endo compared
Université de Strasbourg, Illkirch 67412, France. to the Epi (P=0.002). Vmax was significantly reduced in the
Introduction: Prokineticins are angiogenic hormones that Endo (-16.92%; P=0.04). In presence of increasing NO
activate two G protein-coupled receptors: PKR1 and PKR2. concentration, Vmax were significantly reduced in both layers.
PKR1 has emerged as a critical mediator of cardiovascular Mitochondrial content was similar in Endo and Epi.
homeostasis and cardioprotection. Identification of non-peptide Mitochondrial H2O2 and super oxide anion productions were
PKR1 agonists that contribute to myocardial repair and collateral significantly increased in Endo compared to Epi.
vessel growth hold promises for treatment of heart diseases. Conclusion: increased NO in the subendocardium of left
Material and Methods: Through a combination of in silico ventricle is associated with decreased mitochondrial respiratory
studies, medicinal chemistry, and pharmacological profiling capacities and increased ROS production. The deleterious effects
approaches, we designed, synthesized, and characterized the first of NO on mitochondrial respiration might explain these results.
PKR1 agonists, demonstrating their cardioprotective activity
against myocardial infarction (MI) in mice. Based on high CO-01-006
throughput docking protocol, 250,000 compounds were MICROVASCULAR DYSFUNCTION OF THE
computationally screened for putative PKR1 agonistic activity, SKIN AS AN EARLY MARKER OF PRIMARY
using a homology model, and 10 virtual hits were
pharmacologically evaluated. HYPEROXALURIA TYPE I LESIONS
Results: One hit internalizes PKR1, increases calcium release Laurence DUBOURG1, Alexandra BRUEL2, Pierre COCHAT3,
and activates ERK and Akt kinases. Among the 30 derivatives of Bruno RANCHIN4, Justine BACCHETTA5, Dominique
the hit compound, the most potent derivative, IS20, was SIGAUDO-ROUSSEL6
1
confirmed for its selectivity and specificity through genetic gain- Hospices Civils de Lyon, 2 Hospices Civils de Lyon, 3Hospices
and loss-of-function of PKR1. Importantly, IS20 prevented Civils de Lyon, 4Hospices Civils de Lyon, 5Hospices Civils de
cardiac lesion formation and improved cardiac function after MI Lyon, 6Biologie tissulaire et Ingénierie thérapeutique, UMR
in mice, promoting proliferation of cardiac progenitor cells and 5305 CNRS/Université Claude-Bernard, Lyon.
neovasculogenesis. Introduction: Primary hyperoxaluria type I (PH1) is a rare
Conclusion: The preclinical investigation of the first PKR1 genetic disorder caused by a deficiency of the liver enzyme
agonists provides a novel approach to promote cardiac alanine-glyoxylate-aminotransferase resulting in an excessive
neovasculogenesis after MI. production of oxalate and its accumulation in organs (kidneys,
blood vessel walls, skin, etc.) leading to severe illness and
disability. Whereas severe symptoms occurred when renal
CO-01-005 function is impaired and when plasma oxalate concentration
LEFT VENTRICULAR TRANSMURAL
5
(Pox) is increased, early markers of organ dysfunction are preterm infants (<32GW), present with defective aldosterone
lacking. Therefore we used a non-invasive method to assess skin secretion while the kidney remains sensitive to aldosterone
microvascular function in young PH1 patients with normal Pox action owing to the transient MR expression in the distal tubule
and without severe renal dysfunction compared to controls. during this period. Conversely, high circulating
Materials and Methods: We assessed skin microvascular cortisol/corticosterone levels along with detectable renal
function by laser Doppler flowmetry before and after stimulation glucocorticoid receptor were present at birth, consistent with
by pressure (PIV), thermal or pharmacological (nitroprussiate, functional glucocorticoid-signaling pathway both in preterm and
SNP or acetylcholine, Ach) stimuli in five young PH1 patients full-term newborns. Thus, there exists a defective
compared to controls (n=68). The non parametric test Mann mineralocorticoid signaling from two different mechanisms in
Whitney was used as statistical method. preterm and full-term newborns, whereas renal glucocorticoid
Results: PH1 and controls were age-matched. In PH1, signaling is functional and very likely implicated in fetal
glomerular filtration rate was >75ml/min/1.73m2, Pox was programming.
normal. Nerve tactile sensitivity was decreased in PH1 children Discussion/conclusion: Better understanding of renal
compared to controls (p=0.02). The smooth muscle capacity to corticosteroid signaling in the neonatal period should improve
vasodilate was not different between groups. Ach response was management of neonates and may bring new insights into the
increased in PH1 (p=0.04) as well as the thermal response (initial pathophysiology of adult diseases.
peak (p=0.03) and delayed plateau (p=0.04). However PIV was
not significantly decreased (p=0.09). Invited lecture
Discussion/Conclusion: PH1 patients have an exacerbated
endothelial dependent vasodilation and thermal-induced REPOSITIONING MINERALOCORTICOID
vasodilation suggesting an early dysfunction of the RECEPTOR ANTAGONISTS: PHYSIO-
microcirculation. We need to confirm these results and to go PATHOLOGICAL BASIS AND THERAPEUTIC
further to decipher the mechanisms involved. IMPLICATIONS
Frederic JAISSER,
Nephrology/Endocrinology/ INSERM U1138 team1, Cordeliers Research Center, Pierre-
Marie Curie University, 75006 PARIS, France
Metabolism The mineralocorticoid receptor is a ligand-activated transcription
factor involved in renal ion homeostasis and blood pressure
control. The MR is also expressed in non-renal targets such as
Invited lecture heart, vessels, adipose tissue and immune cells where its role
RENAL CORTICOSTEROID SIGNALING remains to be defined. Pharmacological MR antagonists like
PATHWAYS DURING THE NEONATAL spironolactone, canrenoate and eplerenone are used for decades
PERIOD: CONSEQUENCES ON HYDRO- in patients with hypertension or, more recently, with heart
failure. Therefore pharmacokinetic and toxicology profiles have
MINERAL HOMEOSTASIS been extensively studied. Contra-indications in the nephrology
Laetitia MARTINERIE1,2, Eric PUSSARD1,3,4, Say field in particular context like acute renal ischemia or chronic
VIENGCHAREUN , Pascal BOILEAU , Marc LOMBES1,3
1,3 5
kidney diseases are mainly related to the absence of specific
1
Inserm, U1185, Le Kremlin-Bicêtre, F-94276; 2Service safety trials. Accumulating data, both at the preclinical (rodent
d’Endocrinologie Pédiatrique, Hôpital Robert Debré, and large animal models) and clinical (safety and interventional
Assistance Publique Hôpitaux de Paris, Paris, F-75019; studies) levels, will allow repositioning of these drugs and their
3
Faculté de Médecine Paris-Sud, UMR-S1185, Univ Paris-Sud use in novel clinical indications where, for example,
11, Le Kremlin-Bicêtre, F-94276; 4Service de Génétique microvascular function and hemodynamics are central. I will
Moléculaire, Pharmacogénétique et Hormonologie, Hôpital de describe the role of aldosterone and mineralocorticoid receptor
Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin activation in vascular function and will focus on the
Bicêtre, F-94275; 5Service de Réanimation Néonatale, CH microvasculature underlying the physiological and
Poissy Saint-Germain-en-Laye, Poissy, F-78303, France. pathophysiological role of vascular MR in retinal and renal
Introduction: The neonatal period is characterized by high injuries where alteration of local hemodynamics is important
urinary sodium loss, notably in preterm infants, suggesting that (eye diseases, acute kidney injury, cyclosporine nephrotoxicity)
aldosterone is unable to stimulate sodium reabsorption and as well as future plan for repositioning MR antagonists in
maintain adequate hydro-mineral balance. ischemic kidney diseases and renal transplantation.
Materials and Methods: Plasma and urinary aldosterone levels
were measured in full-term and preterm infants, and correlated
with urinary sodium excretion in a prospective cohort study. CO-04-001
Expression of several actors of the mineralocorticoid and CITRULLINE INDUCES ENERGY
glucocorticoid signaling pathways were also evaluated during EXPENDITURE IN CULTURED EXPLANTS
kidney development, using quantitative PCR, western blot and FROM RAT ADIPOSE TISSUE
immunohistochemistry, in human and mouse renal samples. Nolwenn JOFFIN1, Anne-Marie JAUBERT2, Jessica BAMBA3,
Results: We demonstrate that neonatal sodium wasting is Sylvie DURANT4, Robert BAROUKI5, Xavier COUMOUL6,
associated with a physiological renal aldosterone resistance in Claude FOREST7, Philippe NOIREZ
relation to a low renal mineralocorticoid receptor (MR) 1
INSERM UMR-S 1124, Université Paris Descartes, Sorbonne
expression at birth in full-term infants, both in humans and mice, Paris Cité , 2INSERM UMR-S 1124, Université Paris Descartes,
along with a down regulation of other mineralocorticoid Sorbonne Paris Cité, 3INSERM UMR-S 1124, Université Paris
signaling key-players (11HSD2, ENaC). Moreover, very Descartes, Sorbonne Paris Cité , 4INSERM UMR-S 1124,
6
Université Paris Descartes, Sorbonne Paris Cité , 5INSERM knock-out mice (dKO).
UMR-S 1124, Université Paris Descartes, Sorbonne Paris Cité, Results: We demonstrated that dKO mice displayed a lower
6
INSERM UMR-S 1124, Université Paris Descartes, Sorbonne blood K+ concentration, a marked increase in plasma renin
Paris Cité , 7INSERM UMR-S 1124, Université Paris Descartes, activity and only slightly higher aldosterone level when
Sorbonne Paris Cité, France. compared with wild-type mice. Immunoblot analyses showed a
Introduction: Sarcopenic obesity associates the loss of muscle marked increase in expression of the epithelial Na + channel
mass and the increase in white adipose tissue (WAT) during ENaC and pendrin. Consistently, increase in urinary Na+
aging. Previous studies showed that citrulline (CIT) excretion in response to amiloride was higher in dKO mice that
administration for three months to aging rats increased muscle in wild-type mice. During NaCl depletion, dKO showed signs of
mass but reduced WAT mass. Our aim was to investigate severe vascular dehydration with increased urine output. Marked
whether CIT directly affected energy expenditure in WAT. hypokalemia was likely responsible for the paradoxical
Methods: Cultured explants from rat WAT were treated with 2.5 decreased aldosterone level in dKO.
mmol/L CIT for 24h. We investigated lipolysis, through non- Conclusion: The deletion of both NDCBE and NCC induces
esterified fatty acid (NEFA) release and the phosphorylation of pronounced hypovolemia accompagnied by hypokalemia that is
hormone-sensitive lipase (pHSL), glyceroneogenesis for NEFA likely the result of ENaC activation. Combined inhibition of
re-esterification, beta-oxidation, and markers of mitochondrial NCC and NDCBE/pendrin system could explain thiazide-
biogenesis (transcription factor A, mitochondrial - TFAM) and induced hypokalemia in some patients. Development of new
thermogenesis (uncoupling protein 1 - UCP1). drugs that could inhibit specifically NCC is therefore of interest.
Results: CIT induced pHSL and was anti-glyceroneogenic
whether rats were young (4 months) or old (25 months). CO-04-003
However, CIT stimulated NEFA release from explants of old rats IL-15 RECEPTORS CONFER B AND T CELL-
but not from those of young rats, because of a selective increase
in the oxidative capacity in the latter tissue. Furthermore, INDEPENDENT RESISTANCE TO SEVERE
selectively in WAT from young rats, TFAM and UCP1 were GLOMERULONEPHRITIS IN MICE
augmented by CIT. Laurent MESNARD1, Eric RONDEAU1, James P. DI SANTO2,
Conlusion: Altogether our results indicate that CIT acts directly Fabien CAMPAGNE3, Florence VASSEUR4, Jean-Christophe
on WAT to increase energy expenditure, but with a reduced BORIES5, Alexandre HERTIG1, Sandrine PLACIER6, Julie
impact on old rats. We suggest that NEFA released from WAT SOHIER7, Xiaoli XU7, Sophie VANDERMEERSCH7,
of old rats are used as energetic substrates by muscles. Our data Dominique CATHELIN7, Yosu LUQUE
1
provide a mechanistic basis for the fat mass reduction observed Urgences Néphrologiques et Transplantation Rénale. Hôpital
after CIT administration. Tenon. Paris, 2Institut Pasteur, Unité Immunité innée and
INSERM U668, Paris, 3Weill Medical College of Cornell
CO-04-002 University, Institute of Computational Biomedicine, New York,
USA, 4INSERM U1020, Université Paris Descartes, Paris,
DELETION OF Na+-DRIVEN Cl-/HCO3- 5
INSERM UMR 1126, Institut Universitaire d'Hématologie,
EXCHANGER (NDCBE) AND Na-Cl CO- Hôpital St. Louis, Paris, 6Unité mixte Inserm-Université UMR S
TRANSPORTER (NCC) CAUSES 1155. Hôpital Tenon, 75020, Paris, France, 7Unité mixte Inserm-
HYPOVOLEMIA AND HYPOKALEMIA Université UMR S 1155. Hôpital Tenon, 75020, Paris, France
Nikita RADIONOV, Anne SINNING, Maximilien JAYAT 1, Introduction: The renal lesions developed during experimental
Baron STéPHANIE 2, Carolina CALDERON1, Nicolas anti-glomerular basement membrane glomerulonephritis (anti-
CORNIèRE3, Juliette HADCHOUEL1, Dominique ELADARI5, GBM-GN), an equivalent to human immune-mediated
Christian HüBNER6, Régine CHAMBREY1 glomerulonephritis, have been classically attributed to
1
INSERM U970, Paris Cardiovascular Research Center, perturbations of T cell functions.
2
Hopital Européen Georges Pompidou, Département de Materials and Methods: We studied the role of IL15 receptors
Physiologie, Assistance Publique-Hopitaux de Paris, 3Hopital in murine kidney by using an anti-GBM model in Rag2-/-, Rag2-
Européen Georges Pompidou, Département de Physiologie, /-c-/-, Rag2-/-IL-2R?-/- and Rag2-/-IL15-/- mice.
Assistance Publique-Hopitaux de Paris , 5Hopital Européen Results: We observed that Rag2-/-, or even Rag2-/-c-/- or Rag2-
Georges Pompidou, Département de Physiologie, Assistance /-IL-2R-/- mice devoid of T/B/NK cells develop a severe anti-
Publique-Hopitaux de Paris, 6Institut fur Humangenetik, GBM-GN. Compared to Rag2-/-, Rag2-/-c-/- and Rag2-/-IL-2R-
University Hospital Jena, Friedrich-Schiller-Universität, /- mice harbor an additional deletion of either the common
Germany. gamma chain (gC) or the interleukin-2 receptor subunit (IL-2R)
Introduction: We recently discovered a novel thiazide-sensitive that should lead to the complete absence of IL-15 signaling.
electroneutral NaCl uptake through ß-intercalated cells of the Using Rag2-/-IL15-/- and bone marrow transplantation
collecting duct which results from the parallel operation of the replenishment in Rag2-/-c-/-, we finally demonstrated a role for
Cl-/HCO3- exchanger pendrin and the Na+-driven Cl-/2HCO3- renal epithelial-expressed IL-15 receptor (gC/IL-2R?) during
exchanger (NDCBE). A role of pendrin in maintaining Na + anti-GBM-GN. As Rag2-/-IL-2R-/- anti-GBM-GN tubular
balance, normal vascular volume and blood pressure is well lesions appear extremely severe compared to Rag2-/-c-/-, we
documented. Our goal was to determine whether NDCBE, as the finally analyzed the nature of the IL-15 renal response in vitro.
functional partner of pendrin, plays a similar role. Single deletion We demonstrated that despite the absence of gC, IL-15 still
of NDCBE caused only subtle perturbations of Na + and K+ induced downstream JAK1/3 phosphorylation. The latter was not
homeostasis since the NaCl cotransporter NCC compensates for observed in the absence of IL-2R, explaining Rag2-/-IL-2R-/-
the inactivation of NDCBE and vice-versa. anti-GBM-GN lesions severity.
Materials and methods: We next generated double Ncc/Ndcbe Discussion/Conclusion: Anti-GBM-GN lesions appear in the

7
absence of lymphocytes and are dependent on unsuspected decreases plasmatic levels of IGF-1 and leptin, with a transient
intrinsic renal-expressed IL-15 receptors responses that appear alteration of median eminence innervation by GHRH neurons in
distinctive of current data found in lymphocytes. 10 days-old pups, inducing therein a permanent pituitary
hypoplasia in somatotrophs cells (GH) by 20 days. We
CO-04-004 hypothesized an alteration of neurons development.
IMATINIB INCREASES PLASMA Materials and Methods: C57B6j GHRH-GFP mice were
matted and litter sizes normalized at birth at 6 or 10 pups per
CREATININE CONCENTRATION dam, in order to have normally-fed or restricted pups during
INDEPENDENTLY OF ANY RENAL FAILURE lactation. In vitro culture of arcuate nucleus explants containing
Emmanuelle VIDAL-PETIOT, Martin FLAMANT1, Thomas GHRH and NPY/POMC neurons were performed from one
STEHLE2, Claude GARDIN3, Philippe ROUSSELOT4, Fideline week-old pups.
SERRANO5, Delphine REA6, Marie-Noelle PERALDI7 Results: We observed that IGF-1 stimulates preferentially
1
Service de Physiologie, DHU Fire, APHP, Hôpital Bichat, GHRH neurons using PI3K/AKT and MEK/ERK signaling
Paris, 2Department of renal physiology, DHU Fire, Bichat pathways, while leptin present a broad effect by stimulating
Hospital, AP-HP, 75018 Paris, 3Department of hematology, GHRH and NPY neurons. Interestingly, GHRH neurons from
Avicenne Hospital, AP-HP, 93009 Bobigny, 4Department of restricted pups seem resistant to the axonal stimulation by both
immuno-hematology, Saint-Louis Hospital, AP-HP, 75010 IGF-1 and leptin.
Paris,5 Department of renal physiology, DHU Fire, Bichat Discussion/conclusion: All together, our results indicate that
Hospital, AP-HP, 75018 Paris, 6Department of immuno- nutrition in early postnatal period in mice programs body growth
hematology, Saint-Louis Hospital, AP-HP, 75010 Paris, through leptin and IGF-1 by stimulating GHRH neurons’ axon
7
Departement of nephrology, Saint-Louis Hospital, AP-HP, elongation.
75010 Paris, France
Introduction: Imatinib is a highly effective tyrosine kinase CO-04-006
inhibitor, especially in Philadelphia (Ph) chromosome-positive
leukemias. Monitoring of renal function is important in Imatinib- THE KIDNEY-SPECIFIC ISOFORM OF WNK1
treated patients, as creatinine-derived glomerular filtration rate (KS-WNK1) REGULATES POTASSIUM
(GFR) has been reported to decrease during the course of BALANCE
Imatinib therapy. Whether creatinine might increase in the Juliette HADCHOUEL, Christelle SOUKASEUM, Maria
absence of a true GFR decline has never been investigated. CHAVEZ-CANALES, Shengnan WU
Materials and Methods: Four patients taking Imatinib INSERM U970 - 56 rue Leblanc, Paris 75015, Paris, France.
underwent GFR measurement (urinary clearance of 51CrEDTA) Introduction: Mutations in the serine-threonine kinase WNK1
and assessment of renal clearance and tubular secretion of result in Familial Hyperkalemic Hypertension, which is due to
creatinine. Data from each patient were compared with those of the overexpression of the kinase isoform of WNK1. However,
20 controls matched for measured GFR, age, gender and WNK1 gives also rise to a kinase-deficient isoform, KS-WNK1
ethnicity. (Kidney-Specific-WNK1). Indeed, KS-WNK1 is expressed only
Results: Part of creatinine clearance due to tubular secretion in the kidney, and more precisely in the distal nephron. In vitro
(CCr-S) was 2.4, 3.1, -1.3 and 2.8 mL/min in the 4 patients vs experiments have suggested that it could regulate several renal
17.7±5.6, 43.0±18.0, 26.3±6.8 and 18.6±5.6 mL/min in their transporters.
respective control populations (p<0.001 in each case). In one Materials and Methods: We have generated and worked on a
patient, the same exploration was repeated after discontinuation mouse model of KS-WNK1 inactivation.
of Imatinib, and evidenced a recovery of tubular secretion of Results: Blood and urine electrolytes of KS-WNK1-/- mice are
creatinine (CCr-S 20.3 vs 17.9±5.2 mL/min, p=0.2). normal. Aldosterone secretion is decreased in KS-WNK1-/- mice
Discussion/conclusion: Imatinib blunts tubular secretion of while renin is not affected. The expression and phosphorylation
creatinine, leading to a marked increase in plasma creatinine of the Na-Cl cotransporter NCC are increased while the
concentration, independently of any renal dysfunction. This expression and cleavage of the epithelial sodium Channel
previously unreported pharmacological property of Imatinib (ENaC) are decreased. These changes resemble those observed
explains at least in part the increase in plasma creatinine in animals subjected to potassium depletion. These data strongly
concentration observed after initiation of this therapy. suggest that potassium balance is altered in KS-WNK1-/- mice.
CO-04-005 We therefore tried to "stress the phenotype" of KS-WNK1-/- mice
LEPTIN AND IGF-I STIMULATE AXON to reveal a potassium imbalance. First, we chronically infused
aldosterone to restore a normal aldosterone level in mutant mice.
GROWTH OF HYPOTHALAMIC GHRH This manoeuvre decreased plasma potassium level in KS-WNK1-
NEURONS. /- mice. Second, KS-WNK1-/- mice were fed a high-sodium diet
Lyvianne DECOURTYE, Erik MIRE1, Maud CLEMESSY1, for 7 days. This again led to hypokalemia in KS-WNK1-/- mice.
Victor HEURTIER1, Tatiana LEDENT1, Patrice MOLLARD2, Conclusion: Our study suggests that there is a tendency towards
Yves LE BOUC1, Laurent KAPPELER1 potassium loss in KS-WNK1-/- mice, which is prevented by a
1
UMRS938, INSERM-UPMC, IHU ICAN, Paris, France, decreased aldosterone secretion. It also suggests that the function
5
CNRS, UMR-5203, Montpellier, France. and physiological regulation of principal cells of the distal
Introduction: Nutrition during lactation programs the activity of nephron, expressing ENaC and ROMK, are perturbed in KS-
the somatotropic axis (GH/IGF-1), which regulates body growth WNK1-/- mice.
during postnatal development and plays an important role on
adult metabolism: an alteration of nutrition during this period
leads to cardiometabolic pathologies later in life. Restriction Respiration
8
 ALVEOLAR EPITHELIAL CELLS BY
CO-03-001 MODULATING HYPOXIC SIGNALING
EPO PLAYS A KEY ROLE IN THE NEURAL Olivier BERNARD, Florence JENY, Valérie VANNEAUX1,
CONTROL OF HYPERCAPNIC Elisabetta DONDY2, Nicolas DARD3, Yurdagül UZUNHAN4,
VENTILATORY REPONSE Carole PLANES5, Hilario NUNES6, Jérôme LARGHERO 7
1
Florine JETON, Aurélien PICHON1, Anne-sophie Centre de Thérapie Cellulaire, Hôpital Saint Louis, Paris,
2
PERRINTERRIN2, Dominique MARCHANT3, Patricia ASIH, UMR INSERM 978, Université Paris 13, PRES Sorbonne
QUIDU4, Alain FRUGIERE5, Laurence BODINEAU6, Jorge Paris Cité, Bobigny, 3Université Paris 13 - Sorbonne Paris Cité,
SOLIZ7, Jean-paul RICHALET2, Nicolas VOITURON2 EA2363, Bobigny, 4Université Paris 13 - Sorbonne Paris Cité,
1
Laboratory Mobility, aging & exercise (MOVE) - EA 6314 EA2363, Bobigny, 5Université Paris 13 – Sorbonne Paris Cité,
Faculty of Sport Sciences University of Poitiers, 2Université EA2363, Bobigny, France, 6 Université Paris 13 - Sorbonne
Paris 13, Sorbonne Paris Cité, UFR SMBH, Laboratoire Paris Cité, EA2363, Bobigny, 7Centre de Thérapie Cellulaire,
“Hypoxie et poumon”, EA 2363, 93017 Bobigny, UMR S1158 Hôpital Saint Louis, Paris, France.
Inserm-UPMC, Neurophysiologie Respiratoire Expérimentale et Introduction: Acute or chronic alveolar injuries provoke
Clinique, Physiologie & Plasticité du Contrôle respiratoire, massive apoptosis of alveolar epithelial cells (AEC) that
3
Université Paris 13, Sorbonne Paris Cité, UFR SMBH, compromises an efficient repair of the alveolar epithelium and
Laboratoire “Hypoxie et poumon”, EA 2363, 93017 Bobigny, leads to lung diseases such as ARDS or IPF. These disorders are
4
Université Paris 13, Sorbonne Paris Cité, UFR SMBH, commonly associated with local alveolar hypoxia aggravating
Laboratoire “Hypoxie et poumon”, EA 2363, 93017 Bobigny, their progression through the stimulation of AEC apoptosis.
5
UMR_S1158 Inserm-UPMC, Neurophysiologie Respiratoire Administration of allogenic mesenchymal stem cells (MSC) has
Expérimentale et Clinique, Physiologie & Plasticité du Contrôle been shown to limit lung inflammation and fibrosis in murine
respiratoire, Faculté de Médecine, 6 UMR S1158 Inserm-UPMC, models of alveolar injury, through a still poorly understood
Neurophysiologie Respiratoire Expérimentale et Clinique, paracrine mechanism. We studied whether MSC could protect
Physiologie & Plasticité du Contrôle respiratoire, Faculté de AEC from hypoxia-induced apoptosis and the mechanisms
Médecine, 7Department of Pediatrics, Centre de Recherche de involved.
I'Hôpital St-François d'Assise (CR-SFA), Centre Hospitalier Materiels and Methods: rat primary AEC were exposed for 4-
Universitaire de Québec (CHUQ), Canada. 48 hrs to normoxia or hypoxia (1.5% O2) in the presence or
Introduction: Erythropoietin (Epo) is involved in the hypoxic absence of human MSC conditioned medium (hMSC-CM). AEC
ventilatory response but its effect on the hypercapnic ventilatory apoptosis and reactive oxygen species (ROS) accumulation were
response remains to be determined. The objective was therefore assessed by flow cytometry. Expression of hypoxia-inducible
to assess the role of Epo on the ventilatory response to transcription factors (HIF) and their targets were studied by
hypercapnia (HcVR) and establish if Epo has an effect on immunoblotting and qPCR.
peripheral and/or central ventilatory pathways. Results: hMSC-CM significantly reduced hypoxia-induced
Methods: HcVR was evaluated by whole body plethysmography apoptosis of AEC. Such a anti-apoptotic effect was also obtained
on intact Epo-deficient (Epo-TAgh) mice and intact or with ROS scavenger N-acetylcystein or HIF1a inhibitor YC-1.
chemodenervated wild type (WT) mice after intravenous (IV) or hMSC-CM decreased the protein expression of HIF1 and HIF2
intracisternal (IC) injection of Rhu-Epo. Furthermore, and of their pro-apoptotic target Bnip3 in hypoxic AEC. hMSC-
histological approach was used to determine the respiratory areas CM also reduced ROS accumulation in hypoxic AEC by
involved in this process. enhancing the activity of anti-oxidant enzymes and prevented the
Results: In normocapnia, female Epo-TAgh had higher induction of CHOP, a pro-apoptotic factor induced by ROS
ventilation compared to other groups. In hypercapnia, WT and signaling. The paracrine effect of hMSC was partly dependent
Epo-TAgh mice showed hyperventilation but we observed on KGF and HGF secretion.
different ventilatory patterns between WT and Epo-TAgh: Discussion/Conclusion: hMSC prevent via a paracrine effect
hypercapnia induced an increase of tidal volume in WT and an hypoxia-induced apoptosis of AEC by modulating hypoxic and
increase of tidal volume associated with an increase of breathing ROS signaling.
frequency in Epo-TAgh. Histological approach showed that
several brainstem areas involved in CO2 response were normally
activated in WT mice but were under-stimulated in Epo-TAgh CO-03-003
mice. Injection of Epo (IV and IC) decreased HcVR only in Epo- QUADRICEPS MUSCLE WEAKNESS AND
TAgh females. ATROPHY ARE ASSOCIATED WITH A
Conclusions: Epo deficiency alters the ventilatory response to DIFFERENTIAL EPIGENETIC PROFILE IN
CO2 due to weak response of the ventral surface of the medulla
and modification of the ventilatory pattern without any ADVANCED COPD
impairment in the quantitative HcVR. This suggests the Joaquim GEA1, Josep ROCA2, Pilar AUSIN1, Juana
implication of other respiratory areas in CO2 response and a MARTINEZ1, Puig-Vilanova ESTER1, Esther BARREIRRO1
1
plasticity of the respiratory network. Moroever, Epo could Pulmonology Department-Muscle and Respiratory System
interact with sexual hormones. Research Unit (URMAR), IMIM-Hospital del Mar, Parc de Salut
Mar, Health and Experimental Sciences Department (CEXS),
Universitat Pompeu Fabra (UPF), Barcelona Biomedical
CO-03-002 Research Park (PRBB), 2Servei de Pneumologia (ICT), Hospital
MESENCHYMAL STEM CELLS REDUCE Clinic, IDIBAPS, Universitat de Barcelona,
HYPOXIA-INDUCED APOPTOSIS IN Introduction: Epigenetic mechanisms regulate muscle mass and
function in models of muscle dysfunction and atrophy. We
9
assessed whether quadriceps muscle weakness and atrophy are underlying mechanisms, we assessed EMT. As expected, ZO-1
associated with a differential expression profile of epigenetic staining was diminished in response to cigarette smoke exposure.
events in patients with advanced COPD. Moreover, TA-65 by itself induce the same effect, whatever the
Patients and methods: In vastus lateralis (VL) of sedentary cigarette smoke status. Under imetelstat treatment, preliminary
severe COPD patients (n=41), who were further subdivided into results showed the persistence of SAR.
those with (n=25) and without (n=16) muscle weakness, and Conclusion: Telomerase activity is important to SAR in the
healthy controls (n=19), expression of muscle-enriched pathogenesis of COPD. The underlying mechanisms are
microRNAs, histone acetyltransferases (HATs) and deacetylases currently under investigation.
(HDACs), growth and atrophy signaling markers, total protein
and histone acetylation, transcription factors, and muscle
structure were explored. All subjects were clinically evaluated. Integrative Biology
Results: Compared to controls, in VL of all COPD together and
in muscle-weakness patients, expression of miR-1, -206, and - Invited lecture
27a, levels of lysine-acetylated proteins and histones, and MITOCHONDRIAL PHENOTYPIC
acetylated histone 3 were increased, while expression of
HDAC3, HDAC4, sirtuin-1, IGF-1 were decreased, Akt FLEXIBILITY ENHANCES ENERGY
expression did not differ, follistatin expression was greater, SAVINGS IN FASTING BIRDS
whereas myostatin expression was lower, serum reponse factor Roussel D, Monternier PA, Fongy A, Romestaing C,
(SRF) expression was increased, and fiber size of fast-twitch Bourguignon A, Rouanet JL, Duchamp C, Voituron Y. LEHNA,
fibers was significantly reduced. In VL of severe COPD patients UMR 5023 CNRS, Université de Lyon, Villeurbanne, France.
with muscle weakness and atrophy, epigenetic events regulate Introduction: Energy conservation is a key priority for
muscle differentiation rather than proliferation, and muscle organisms having to face seasonal or stochastic shortages in
growth and atrophy signaling, probably as feedback mechanisms resource supplies. Because mitochondrial bioenergetics
to prevent those muscles from undergoing further atrophy. constitute the functional link between environmental resources,
Lysine-hyperacetylation of histones may drive enhanced protein whole body energy expenditure and animal performances (e.g.
catabolism in those muscles. growth, locomotion, thermoregulation), these organelles may
Conclusion: These findings may help design novel therapeutic represent an important proximate factor responsible for energy
strategies (enhancers of microRNAs promoting myogenesis and savings during fast.
acetylation inhibitors) to selectively target muscle weakness and Materials and Methods: We studied mitochondrial
atrophy in COPD. bioenergetics (oxidative phosphorylation activity, ATP synthesis
efficiency, oxidative capacity) of skeletal muscle mitochondria
CO-03-004 from birds (penguins and ducks) during the course of
fasting/refeeding periods.
TELOMERASE-DEPENDENT MODULATION Results: Bioenergetics analysis of pectoralis and gastrocnemius
OF SMALL AIRWAY REMODELING IN muscles revealed that mitochondria are more energy efficient
CHRONIC OBSTRUCTIVE PULMONARY shortly after the beginning of fast, indicating that skeletal
DISEASE muscles of fasted birds consume fewer nutrients to sustain their
Abdoulaye SAMB1, Sophie LANONE2, Jorge BOCZKOWSKI3, energy-demanding processes. This adjustment of mitochondrial
Philippe CARAMELLE4, Jeanne TRAN VAN NHIEU5, Arnaud efficiency was fully reversed by refeeding and would be under
TIENDREBEOGO the control of thyroid hormones.
1
Servive de Physiologie et d’Explorations Fonctionnelles, Discussion/conclusion: Skeletal muscle mitochondria from
2
Inserm U955 – Team 04, Faculty of Medicine, Creteil, France, fasted birds decrease the cost of ATP synthesis by minimizing
3
Inserm U955 – Team 04, Faculty of Medicine, Creteil, France, the needs for energy substrates. The mitochondrial energy
4
Inserm U955 – Team 04, Faculty of Medicine, Creteil, France, transduction processes prove to be highly flexible, suggesting
5
Department of Pathology, GH Henri Mondor, Creteil, France that birds would adjust the cost of mitochondrial metabolism in
Introduction: Airflow obstruction in chronic obstructive order to cope with their nutritional status.
pulmonary disease (COPD) is associated with two different
anatomical lesions: emphysema and small airway remodeling Invited lecture
(SAR). The pathogenesis of SAR is still an area of discussion but PROTEOMICS AS A WAY TO EXPLORE
may include senescence, notably associated with telomere
shortening. This shortening can be counteracted by telomerase. METABOLIC DISORDERS IN EXOTIC
Our hypothesis is that telomerase activity could be important to SPECIES
SAR. The aim of our study was therefore to address the effects BERTILE Fabrice
of the positive or negative modulation of telomerase activity CNRS, UMR7178, IPHC Département Sciences Analytiques,
(TA-65 or Imetelstat respectively) on the development of SAR Strasbourg
in a cigarette smoke murine model of COPD. Over the last 20 years, mass spectrometry-based proteomics has
Methodology: SAR was quantified by morphometric analysis. become an indispensable tool in the cellular and molecular life
Lung tissues were examined by immunohistochemistry for sciences to identify, quantify and characterize proteins.
matrix deposition and epithelia-mesenchymal transition (EMT). Nowadays, it allows thousands of proteins to be analysed
Results: Exposure to cigarette smoke induced SAR, with an simultaneously, both in sequenced and non-model (not or not
increased collagen deposition and alpha-SMA expression in well represented in protein databases) species. The aim is here to
small airways (SA), but no mucus overproduction. Pretreatment present examples where proteomics applied to exotic species can
with TA-65 prevented this SA fibrosis. To understand the help understanding how certain wild animals do support

10
environmental conditions that would be detrimental to human (CRICETUS CRICETUS)
health. We notably examined the impact of different conditions Caroline HABOLD1, Hugues OUDART2, Mathieu WEITTEN3
1
(e.g. food scarcity, weightlessness and physical inactivity, high- Université de Strasbourg, IPHC, 2 Université de Strasbourg,
fat diets) on the proteome of various tissues collected in wild IPHC, 3Université de Strasbourg, IPHC
penguins, wild bears and selected lines of voles. This was Introduction: To limit energy expenditure during harsh winter
achieved through a combination of different complementary conditions (drop in ambient temperature and food scarcity),
proteomics methods, and the use of home-developed software hibernating species perform torpor bouts characterized by a
suites dedicated to proteomics data analysis. We found drastic decrease in body temperature and hypometabolism. They arise
differences in the plasma proteome of breeding penguins vs. that periodically from torpor to restore critical functions requiring
of laboratory rats in response to prolonged fasting, in the muscle euthermia. Most species do not feed during hibernation and rely
proteome of mice after a 30-day space flight vs. that of bears after on body reserves to fulfill energy requirements (fat-storing
5 months of physical inactivity, and in the brown adipose tissue species), whereas others hoard food in a burrow (food-storing
(BAT) proteome of voles selected for their BAT activity level species) and feed during intertorpor arousals. Fat-storing species
(high vs. low) in response to a high-fat diet. These data highlight undergo a marked atrophy of the digestive tract, whereas food-
proteomics as a unique analytical strategy to tackle questions storing species have to maintain a functional digestive system
related to human health that simply may not be answered by only during hibernation. The aim of our study was to evaluate
studies in the mainstream of laboratory murine models. precisely the absorption capacities of a food-storing species: the
common hamster, during hibernation.
CO-09-001 Methods: In vivo intestinal perfusions were conducted in
CHARACTERISATION OF MOLECULAR AND different groups of hamsters (n=5): before hibernation, during
CELLULAR MECHANISMS UNDERLYING torpor, during intertorpor arousal, at summer rest. The perfusate
was composed of: 10% Starch, 8.2% proteins, 5% Oils, 0.8%
GLUCOCORTICOID-INDUCED MUSCLE Minerals and 76% saline (expressed as percentage of mass)
ATROPHY. Results: Triglyceride and starch hydrolysis were similar in
Vanessa UEBERSCHLAG, Delphine DUTEIL1, Gilles hibernating (torpid and arisen) and non-hibernating hamsters.
LAVERNY1, Maxime PARISOTTO1, Laetitia PONCET1, Also, intestinal free fatty acid absorption was similar in all
Arnaud FERRY2, Daniel METZGER1 groups, whereas glucose absorption was 40% higher in hamsters
1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, during torpor and arousal compared
CNRS UMR 7104, INSERM U964, Université de Strasbourg, to non-hibernating animals.
2
Université Pierre et Marie Curie, Sorbonne Universités, CNRS Conclusions: Contrasting with fat-storing species, intestinal
UMR 7215, INSERM U974, Institut de Myologie, Université absorption capacities of food-storing species are maintained and
Paris Descartes, France. even increased (for glucose) during hibernation in order to
Introduction: Glucocorticoids (GC) are stress hormones that optimize nutrient assimilation during short intertorpor arousals.
exhibit potent anti-inflammatory properties. High levels of GC The mechanisms enabling increased glucose absorption during
induce, however, the degradation of muscle proteins, which limit hibernation will be investigated, notably through measuring
their use as anti-inflammatory drugs. The activity of GC is expression of transporters.
mediated through the glucocorticoid receptor (GR), a member of
the nuclear receptor superfamily. CO-09-003
Materials and Methods: To unravel the signalling pathways
controlled by GC in skeletal muscles, we generated and
LOCOMOTOR DYSFONCTION AND
characterised mice in which GR is selectively ablated in skeletal HYPOTONIA IN DOWN SYNDROME MOUSE
muscle myofibers at adulthood. Moreover, to identify the MODELS FOR THE HSPA13-APP REGION AS
underlying molecular mechanisms, we performed transcriptomic A CONSEQUENCE OF DOSAGE SENSITIVE
analyses of murine skeletal muscles and chromatin GENES CONTROLLING MUSCULAR
immunoprecipitations followed by massive sequencing.
Results: Our data demonstrate that GC, via myofiber GR, impair
METABOLISM AND MITOCHONDRIAL
protein synthesis and promote protein degradation in skeletal FUNCTION
muscles. In addition, our analyses reveal that a number of genes Véronique BRAULT, Caroline ROMESTAING1, Ignasi
involved in proteolysis, apoptosis and transcriptional regulation SAHUN, Mona KAROUT2, Christelle BOREL3, Doulaye
are selectively up-regulated by GC via myofiber GR, including DEMBELE4, Jean-Charles BIZOT5, Nadia MESSADDEQ6,
many that were not previously reported to be glucocorticoid Andrew J SHARP7, Damien ROUSSELL8, Stylianos E
targets in skeletal muscles. ANTONARAKIS9, Mara DIERSSEN10, Yann HERAULT11
1
Conclusion: The identification of the signalling pathways LEHNA, CNRS UMR502, 2IGBMC, 3Department of Genetic
controlled by GC in myofibers provides important insights into Medicine and Development, University of Geneva Medical
the regulation of muscle mass, and might facilitate the School, 4IGBMC, 5Key-Obs S.A., 6IGBMC, 7Department of
development of new drug targets to combat muscle wasting. Genetics and Genomic Sciences, Mount Sinai School of
Moreover, further characterisation of direct GR target genes will Medicine, 8LEHNA, CNRS UMR502, Université de Lyon,
9
open new avenues to select GC with increased tissue selectivity. Department of Genetic Medicine and Development, University
of Geneva Medical School, 10Genes and Disease Program,
CO-09-002 Center for Genomic Regulation, 11IGBMC UMR7104
Introduction: Aneuploidies of human chromosome 21 (Down
INTESTINAL ABSORPTION CAPACITIES OF syndrome and monosomy 21) lead to variable physiological
HIBERNATING EUROPEAN HAMSTERS abnormalities, with constant mental retardation and delayed

11
locomotor skills. Delayed motor performance, weak muscle need for a more « thermogenic », loose-coupled mitochondria in
strength and exercise limitation observed in individuals with cold-acclimated ducklings.
Down syndrome are not yet understood and remain a challenging
issue. CO-09-005
Material and Methods: We created mouse models of trisomy THE AGE-PERFORMANCE RELATIONSHIP:
(Ts3Yah) and monosomy (Ms3Yah) for carrying respectively a
tandem duplication and a deletion of the Hspa13-App interval TOWARD A NEW MODEL
syntenic with 21q11.2-q21.3. Those models were submitted to a Vincent FOULONNEAU, Geoffroy BERTHELOT, Jean-
battery of phenotypic tests that revealed changes in muscle François TOUSSAINT, Adrien MARCK, Guillaume
strength, motor function and endurance. We further investigated SAULIèRE, Adrien SEDEAUD, Juliana ANTERO-
muscle physiology using histology, microarray hybridization and JACQUEMIN, Julien SCHIPMAN, Andy MARC
mitochondrial metabolism. Institut National du Sport, de l'Expertise et de la Performance,
Results: The expression profiling of skeletal muscles revealed 11 Avenue du Tremblay, 75012 Paris, France.
global changes in the regulation of genes implicated in energetic Introduction: The physiological traits characterizing human
metabolism, mitochondrial activity and biogenesis. These genes capacities (the ability to move, reproduce or perform tasks) vary
are downregulated in Ts3Yah mice and upregulated in Ms3Yah with age: performance is limited at birth, increases to a
mice. The shift in skeletal muscle metabolism correlates with a maximum, then decreases back to zero at death. Both physical
change in mitochondrial proliferation without an alteration in the and intellectual skills follow similar ontogenies.
respiratory function. However, the reactive oxygen species Materials and Methods: Here we aim at accurately describing
(ROS) production from mitochondrial complex I decreased in the asymmetrical age-performance pattern observed in various
Ms3Yah mice, while the membrane permeability of Ts3Yah physiological and biological phenomena. We introduce a
mitochondria slightly increased. tractable model based on biological assumptions that includes
Conclusion: Our findings demonstrate that one or more gene(s) two fonctions, respectively related to the rate of cell division and
present within the Hspa13-App region are implicated in the the decrease of performance with ageing.
regulation of muscle energy metabolism and integrity, and point Results: The model was well adjusted (all adjusted R² > 0.9) to
at a defect in the mitochondrial respiratory chain. major physiological functions in various biological settings and
describes the link between maximal capacity, age at peak
performance and senescence parameters.
CO-09-004 Discussion/Conclusion: The new model provides a good
MITOCHONDRIAL EFFICIENCY AS A estimation of the whole development of performance throughout
REGULATOR OF ENERGY TRADE-OFFS IN lifespan. It is consistent with earlier works that focused on the
BIRDS FASTING IN THE COLD decrease of performance with ageing and gives the best
Pierre-axel MONTERNIER, Anaïs FONGY1, Loïc TEULIER2, approximation of the performance at advanced ages. The future
Jean-Louis ROUANET3, Jocelyne DRAI4, Delphine COLLIN- inclusion of theoretical physics may lead to shed light on the
CHAVAGNAC5, Frédéric HERVANT 6, Damien ROUSSEL7 ageing dynamics at the cellular scale.
1
LEHNA UMR 5023, 2LEHNA UMR 5023, 3LEHNA UMR 5023,
4
CarMen INSERM 1060, 5Centre Hospitalier Universitaire Lyon CO-09-006
Sud, 6LEHNA UMR 5023, 7LEHNA UMR 5023 UPREGULATION OF RYANODINE
Introduction: During food shortage, energy conservation is a
key priority for organisms. We have recently provided evidences RECEPTOR EXPRESSION INCREASES THE
that flexibility in the mitochondrial oxidative phosphorylation CALCIUM-INDUCED CALCIUM RELEASE
(OxPhos) efficiency may represent a key factor responsible for AND SPONTANEOUS CALCIUM SIGNALS IN
the energy conservation and the remarkable fasting endurance of CEREBRAL ARTERIES FROM HINDLIMB
king penguin chicks during winter. UNLOADED RATS
Material and Methods: We investigated mitochondrial OxPhos Jean-luc MOREL, Yves PORTE, Fabrice DABERTRAND,
adjustments of a mature (gastrocnemius) and immature skeletal Anne PREVOT, Nathalie MACREZ
muscle (pectoralis) in fasting Muscovy ducklings either CNRS UMR 5017, Université de Bordeaux II, Bordeaux 33078,
chronically exposed to cold or reared at thermoneutrality. This France.
protocol was designed to study the energetic constraints (cold Introduction: Microgravity induces a redistribution of blood
and starvation) independently. volume. Consequently, astronauts’ body pressure is modified so
Results: In cold-acclimated fasted ducklings, OxPhos capacity that the upright blood pressure gradient is abolished, thereby
decreased in both skeletal muscles, but only pectoral muscle inducing a modification in cerebral blood pressure. This effect is
mitochondria were more efficient at producing ATP. In mimicked in the hindlimb unloaded rat model. Because Ca2+
thermoneutral fasted ducklings, the decreased activity of OxPhos signals could be considered as an index of the vascular reactivity,
was concomitant with an increased OxPhos efficiency in both we have compared the signals obtained in cerebral arteries from
skeletal muscles. These adjustments remain after fasted control and hindlimb unloaded animals.
ducklings were acutely exposed to cold. Materials and Methods: The Ca2+ signals were measured with
Discussion/Conclusion: On the whole, these results highlight Fluo8-AM fluorescent Ca2+ probe, loaded ex vivo in cerebral
the fact that cold acclimation impairs mitochondrial adjustment arteries and the expression of ryanodine receptors was explored
of OxPhos efficiency in gastrocnemius, an early functional by RT-qPCR, immunostaining and western blots.
muscle which is involved in avian thermogenesis. In conclusion, Results: After a duration of 8 days of unloading, Ca2+ signals
we suggest that starvation-induced energy sparing in activated by depolarization and inositol-1,4,5-trisphosphate
gastrocnemius is counterbalanced by cold acclimation and the intracellular release were increased in cerebral arteries. In
12
presence of ryanodine and thapsigargin, the depolarization- REACTIVE ANXIETY AND DEPRESSIVE-
induced Ca2+ signals remained increased in hindlimb suspended LIKE BEHAVIORS IN NEUROPATHIC MICE
animals, indicating that Ca2+ influx and Ca2+-induced Ca2+ Nisrine KAMOUN
release mechanism were both increased. Increases in both University of Strasbourg, Institut des Neurosciences Cellulaires
amplitude and frequency of spontaneous Ca2+ waves were et Intégratives (INCI), France.
measured in hindlimb suspension conditions. After Introduction: Neuropathic pain is associated with significant
pharmacological segregation of Ca2+ sparks and Ca2+ sparklets, co-morbidity, including anxiety and depression. Several lines of
we show an increase in their frequencies, suggesting an increase evidence suggest that anxiolytics may be of interest to alleviate
of excitability. Expressions of L-type Ca2+ channels and pain symptoms and the associated negative emotions in chronic
ryanodine receptor subtype 1 (RyR1) were increased in hindlimb pain states. Among them, the non-benzodiazepine anxiolytic
unloading conditions. etifoxine (EFX: stresam™) has an interesting pharmacological
Conclusion: These results suggest that RyR1 expression and profile. In this study, we aim to analyze the preclinical
voltage-dependent Ca2+ channels activity are the focal points of therapeutic potential of etifoxine on the anxiodepressive
the regulation of Ca2+ signals activated by vasoconstriction in rat consequences of neuropathic pain.
cerebral arteries with an increase of the voltage-dependent Methods: Neuropathic pain was induced by the implantation of
Ca2+ influx. a cuff around the main branch of the sciatic nerve in mice.
Neurophysiology Mechanical allodynia was evaluated with von Frey filaments.
Spontaneous pain was assessed by the conditioned place
preference (CPP) test for clonidine analgesia. Two weeks after
CO-02-001 cuff implantation, EFX treatment (or vehicle) was administered
COMPARISON OF THE CHARACTERISTICS daily and for 5 days, at a reference dose of 50mg/kg
OF ISCHAEMIC STROKES IN CANNABIS (Intraperitoneal). Anxiety and depressive like behaviors were
USERS VERSUS NON-CANNABIS USERS IN A evaluated by a battery of behavioral tests including novelty
PROSPECTIVE SERIES OF 334 YOUNG suppressed feeding, marble burying, splash and forced swim test.
Results: Mechanical allodynia resulting from the compression
PATIENTS of the sciatic was fully abrogated after 2-3 daily injections of
Ielyzaveta ZINCHNEKO1, Valérie LAUER1, Olivier etifoxine and allodynia never reappeared after the 5-day
ROUYER1, Christian MARESCAUX1, Bernard GENY2, Valerie treatment for at least 90 days. Etifoxine analgesia was further
WOLFF1 confirmed using the CPP test since EFX-treated mice did not
1
Unité neuro-vasculaire, Service de Neurologie, Hôpitaux show a preference for clonidine analgesia. Compared to vehicle-
universitaires de Strasbourg, 2EA3072, Université de treated mice which all exhibited anxious and depressive-like
Strasbourg, Fédération de Médecine Translationnelle de behaviors.
Strasbourg, 67000 Strasbourg, France Conclusions: Our results showed that a 5-day treatment with
Introduction: Cannabis has recently been described as a risk EFX not only suppressed pain symptoms and spontaneous pain
factor for stroke in the young. The aim of this study was to behaviors, but also prevented the anxiodepressive consequences
compare the characteristics of ischaemic stroke (IS) in cannabis of this neuropathic pain state.
users (CU) versus non-cannabis users (NCU).
Methods: We have prospectively studied 334 young patients
between 2005 and 2014 with an acute IS. The patients were CO-02-003
investigated by a standardized protocol including biological and GIFTEDNESS: AN ELECTROPHYSIO-
urinary toxicological screenings, cardiac and vascular check up. LOGICAL INVESTIGATION OF
We specifically studied the characteristics of patients with IS HEMISPHERIC SPECIALISATION
among CU in comparison to NCU. Marie-noële MAGNIé-MAURO, Bernadette BAILET
Results: Fifty-five of 334 (16.5%) IS patients were CU. Mean Pôle des Neurosciences Cliniques, CHU de Nice.
age was 34.2±1.1 in CU (sex ratio 2.66) and 37.2±0.4 (sex ratio Introduction: The current study aimed at further tracking the
0.9) in NCU, p<0.05. Cannabis use was more frequently neurophysiological correlates of giftedness. Whereas
associated with other lifestyle risk factors as tobacco (96.4%) and electrophysiological studies provided evidence for an
alcohol use (45.4%) than in NCU (in respectively 40.5% and accelerated cognitive maturation in gifted children, behavioural
9%). The more frequent aetiology of IS in CU was intracranial studies argue for particularities in hemispheric lateralisation. The
arterial stenosis in 47.2% (vs 13% in NCU). The other aetiologies Event-Related Potentials (ERPs) were recorded in order to
were cardioembolism in 16.3% (vs 36.5%), cervical dissection in investigate hemisphere specialisation in giftedness.
7.2% (vs 13.3%), haematological in 3.6% (vs 4.6%), small vessel Materials and Methods: The ERPs were recorded from 50
disease in one case (vs 2 cases) and atherosclerosis in 2 cases (vs right-handed children ranged from 8 to 12 years divided into two
4%). Clinical outcome at 3-month was favourable with a mRS age-matched groups: 25 gifted children, and 25 controls. All the
inferior to 2 for 84% of patients CU vs 77% in NCU, NS. children performed a neuropsychological set including the
Conclusions: CU with IS are younger and other lifestyle risk Intellectual Quotient (IQ) assessment. The EEG was recorded
factors are more represented in this subgroup comparing to NCU. from 26 electrodes, while children performed a decision task and
Intracranial arterial stenosis is the most frequent aetiology of a matrix completion task using the divided visual field technique.
stroke in CU. Results: The ERP analyses showed significant differences in
both the N400 and the P300 latency bands during the two tasks
CO-02-002 arguing for an enhanced right hemisphere involvement. The
ETIFOXINE EFFECTS ON PAIN SYMPTOMS, pattern of ERPs demonstrated particularities in the hemispheric
specialisation as a function of the IQ profile.
13
Discussion/conclusion: The present investigation is in line with the ambiguity of the visual cue embedding the reward status, we
the cognitive style usually observed in giftedness favouring successfully modulated animal certainty and created doubt.
holistic rather than analytic information processing with higher Behavioral results showed that the animal uncertainty level
abilities to perform simultaneous rather than sequential influenced not only performances and reaction times but also
processes. Assessing the cognitive style of gifted children using checking behavior. Fronto-central EEG potentials were also
neurophysiological investigations permits to better understand modulated by ambiguity detection and checking initiation. Daily
their pedagogic needs. cortisol quantification revealed a positive correlation between
monkey checking behavior and anxiety level.
CO-02-004 Conclusion: Taken together, our study demonstrated that
HIGH FREQUENCY RTMS STIMULATION IN theCheck-or-Go task is a valid behavioral toolto study the impact
of ambiguity on doubt and its subsequent adaptive checking
ORO-FACIAL PAIN function and will thereby help us provide new insights into OCD
Richard ROKYTA1, Jitka FRICOVA2 mechanisms.
1
Charles University in Prague, Third Faculty of Medicine,
Department of Physiology, 2Charles University in Prague, First
Faculty of Medicine, Pain Management Center, Czech Republic. CO-02-006
Introduction: Theta burst stimulation (TBS) is a modification PUPILLOMETRY AND HEARING LEVEL
of the application using high-frequency TMS discharge (i.e. DETERMINATION IN NORMAL HEARING
burst) by 3-5 stimuli at a frequency of 50 Hz applied repeatedly AND COCHLEAR-IMPLANTED SUBJECTS
every 200 ms. David BAKHOS, Soo KIM1, Frédérique BONNET-
The goal of the study was 1) to demonstrate the effect of TBS in BRILHAULT2, Nadia AGUILON2, Joêlle MARTINEAU2
patients with the syndrome of chronic orofacial pain. The 1
Faculté de médecine de Tours, 2INSERM U930, Tours, France.
application of intermittent TBS (ITBS) on the contralateral Introduction: Cochlear implant (CI) fitting is difficult, as there
motor cortex in the corresponding somatotopic localization of is no objective measure of hearing level. Variation in pupil size
pain. Methods: The study included 19 patients (12 females, 7 has been associated with mental processing load and/or sensory
males) with chronic, treatment resistant orofacial pain with a discomfort. This study seeks to develop a new objective measure
duration of illness of at least 6 months with stable analgesic of hearing level in CI users by measuring pupil size during a
medication. Clinical trials used subjective VAS ranging from 0 listening task.
to 10 points and QST setting the threshold for thermal and tactile Materials and Method: Fourteen adult post-lingually deafened
(touch) sensation in the affected facial area. cochlear implant (CI) users (mean age 46 yrs, ±19), as well as a
Results: VAS: it was found the statistically significant effect of control group of normal hearing (NH) listeners (mean age 25
theta stimulation (p=0.000068) Thermic stimulation: The results yrs±4) participated in the study. Patients were presented with 4
obtained by ANOVA for repeated measurements are not lists of 10 spoken French words at 4 different intensities (30, 50,
statistically significant change.Tactile stimulation is close to 70, 90 dB SPL). Pupillometry data were recorded using an eye-
statistical signifikance by using the Anova methods. tracking system. We investigated the latency and amplitude of
Conclusion: From our study, we can conclude that the theta dilation and constriction, the dynamic range of pupil size
burst stimulation can be used as a useful tool of the treatment of between dilation and constriction, and the relative peak of
orofacial pain. dilation (i.e., maximum peak dilation normalized to the dynamic
range). All data were compared to the baseline.
CO-02-005 Results: Amplitude of the dilation peak, dilation relative peak
MONKEYS DOUBT AND CHECK and mean pupil size were related to the intensity across groups.
Marion BOSC, Bernard BIOULAC, Nicolas LANGBOUR, Tho- Significant differences were observed for the mean size and peak
Hai NGUYEN, Michel GOILLANDEAU, Benjamin DEHAY, amplitude of dilation between 30 dB and 90 dB SPL. No
Pierre BURBAUD, Thomas MICHELET significant differences were observed among presentation levels
IMN CNRS 5293, Université de Bordeaux, Bordeaux, France. in terms of dilation or constriction latency for the CI or NH
Introduction: Checking compulsions is among the most groups.
common behavioral features of obsessive-compulsive disorder. Conclusion: Pupil dilates with increasing intensity, suggesting
Checking compulsion is thought to be a behavioral attempt to that pupillometry may be a useful measure of discomfort
relieve anxiety caused by high levels of doubt and uncertainty. threshold during CI fitting, especially for very young CI users.
The physiology of checking behavior remains poorly understood
and no concrete and reliable model of physiological checking has
been developed so far. The present behavioral study tends to
Nutrition/Food
characterize physiological doubt and checking behavior in non- Science/Gustation
human primates (NHP).
Methods: To do so, we designed a novel behavioral task to study
electrophysiological correlates of decision making, doubt and Invited lecture
checking in NHP. We trained two rhesus monkeys at the Check- AMINO ACID SENSING: THE EIF2A
or-Go task while recording their frontal EEG signal. We also SIGNALING IN HEALTH AND DISEASE.
collected saliva samples to quantify cortisol along sessions to FAFOURNOUX Pierre, AVEROUS Julien, BRUHAT Alain,
correlate anxiety level with checking behavior. CARRARO Valérie, JOUSSE Céline, MAURIN Anne-
Results: Our experimental paradigm allows the animal to Catherine, PARRY Laurent
multiple-check and change the availability of a reward before Equipe Gènes-Nutriments, Unité de Nutrition Humaine, INRA
taking the final decision leading to that reward. By manipulating de Clermont-Theix, France.
14
In mammals, nine amino acids are qualified as essential (EAA) EXPRESSION IN YOUNG RAT SALIVARY
since they cannot be synthetized endogenously and thus must be GLANDS
supplied by the food. Therefore complexes mechanisms execute Martine MORZEL, Hélène BRIGNOT, Marie-Chantal
a fine control of amino acids homeostasis in case of a dietary CANIVENC-LAVIER, Vincent PAILLé, Patricia PARNET,
protein scarcity. We deciphered the signaling mechanisms that Sophie NICKLAUS
underline the control of gene expression and physiological INRA, CSGA, Dijon, France.
functions by nutritional limitation in EAA. More particularly, we Introduction: Early nutrition through maternal diet during
have shown that AAE limitation activates a signaling pathway pregnancy and breastfeeding was shown to have an impact on
that include the protein kinase GCN2, the translation initiation obesity in childhood. Experiments on animal models have also
factor eIF2α and the transcription factor ATF4 which binds the indicated alterations regarding taste preferences. In addition,
Amino-Acid Response Element (AARE) to turn-on salivary physiology has a documented role in taste preferences
transcription. In response to dietary amino acid deficiency, the and food intake in rodents. The objective of this study was
brain-specific activation of the eIF2a kinase GCN2 leads to food therefore to study the impact of maternal diet on salivary glands’
intake inhibition. Precisely, the sole phosphorylation of eIF2 in protein profiles of the offspring.
the mediobasal hypothalamus is sufficient to regulate food Materials and methods: Female rats received during gestation
intake. Considering that eIF2 phosphorylation is common to and lactation either a control (C) or a high fat / high sugar diet
different stress pathways activated upon several disorders, our (WD for “Western Diet”). 18 offspring rats (9C/9WD) were
data suggest that eIF2 signaling in the hypothalamus could play sacrificed at 25 days of age, i.e. shortly after weaning. Protein
an important role in various pathologies leading to anorexia. expression in their submandibular glands was studied by 2D
electrophoresis, and proteins differentially expressed (p<0.05)
Invited lecture between the two groups were identified by LC-MS/MS.
INTERACTIONS BETWEEN FOOD INTAKE, Results: Out of 413 spots detected and semi-quantified, 16 spots
METABOLISM AND CIRCADIAN CLOCKS were differentially expressed between WD and C young rats. The
CHALLET Etienne submandibular glands of WD animals were characterized in
Institute of Cellular and Integrative Neurosciences, CNRS particular by a higher abundance of proteins with chaperone
UPR3212, University of Strasbourg, Strasbourg, France. functions (Hsc70, HSP60, protein disulfide isomerase), annexin
Introduction: Biological functions show daily rhythms, A6, proteasome, or enzymes previously described as responding
including feeding /lipogenesis during the active period and to nutrient intake (2-oxoisovalerate dehydrogenase,
fasting/lipolysis during the rest period. This temporal adenosylhomocysteinase).
organization is controlled by a multi-oscillatory circadian timing Discussion/conclusion: We here demonstrate the plasticity of
system. Timed feeding is a synchronizer for secondary clocks in offspring salivary glands in response to maternal diet. The link
peripheral organs, such as the liver, but not for the master clock with saliva secretion and ingestive behaviour (sweet and fat
located in the suprachiasmatic nucleus of the hypothalamus reset preference) deserves further investigation.
primarily by ambient light.
Materials and Methods: We studied the effects of calorie
restriction and high-fat feeding on circadian rhythmicity. We
also assessed circadian responses in obese (ob/ob) and diabetic
(db/db) mice. Finally, the impact of circadian desyncronization CO-06-002
on glucose metabolism was investigated in the diurnal Grass rats, EFFECT OF HIGH SPINACH (S. OLERACEA)
Arvicanthis. DIET COMPARED WITH CDCL2, CONSUMED
Results: Calorie restriction (ie, when only a hypocaloric diet is WITH OR WITHOUT GREEN TEA
given every day) alters synchronization of the suprachiasmatic
clock to light, via an increased phase-shifts. By contrast, high-fat
DECOCTION ON KIDNEY AND LIVER
diet reduces light-induced phase-shifts. The db/db and ob/ob OXIDATIVE STRESS IN RATS.
mice show differential alterations of photic synchronization. Soumaya GLID, Ali BEN AMOR, Héla JLASSI1, Mohamed
Exogenous leptin can act as chronomodulator in ob/ob mice by Hédi HAMDAOUI2
1
normalizing the phase shifts induced by light. Chronic jet-lag in Unité de Recherche -high School of Health Sciences and
diurnal Grass rats not only causes a circadian desynchronization, Technicals, 2High School of Health Sciences of Tunis, Tunisia.
but also glucose intolerance, indicating a pre-diabetic condition, Introduction: Our objective was to study the effect of Cd
as well as a shortening of telomeres, a biological marker of spinach with or without green tea decoction (GTD) on kidney
cellular aging. and liver oxidative stress in rats.
Discussion/conclusion: In contrast to peripheral clocks that are Materials and Methods: The study included 28 adult male rats
entrained by feeding time, the master clock is rest by light and divided into 4 groups: G1 received standard, diet, G2: standard
modulated by metabolic cues, including leptin. In addition, diet +CdCl2, G3: standard diet + spinach and G4: standard diet+
metabolic disruptions, such as in db/db and ob/ob mice, induce spinach +GTD. At the end of the experiment, the rats were
circadian disturbances. Conversely, circadian dysfunction is a anesthetized with ether and sacrificed. Blood, liver and kidneys
potential cause for the metabolic syndrome. were collected to determine the retention of Cd, the concentration
of MDA and proteins as biomarkers of oxidative stress in the
CO-06-001 liver and kidneys and the total antioxidant powerful.
Results: The results showed a high content of Cd in the spinach,
CONSEQUENCES OF A HIGH SUGAR/HIGH an average of 7 mg/kg of dry matter. The administration of a diet
FAT MATERNAL DIET ON PROTEIN rich in spinach significantly increased the content of Cd in the

15
organs especially the kidneys (mean 3.5 mg/g fresh weight). In Santé, Morocco.
addition, diets + CdCl2 and/ or spinach significantly increased Introduction: Micronutrients deficiencies are prevalent in
the concentration of hepatic MDA (1 nmol /g) and renal (0.5 Morocco and can affect the mental development and learning
nmol /g) as compared to the control group (0.25 nmol/g). ability of school children. The purpose of this study was to
Conversely, GTD significantly reduced hepatic MDA evaluate the effect of multiple micronutrients fortified milk on
concentration (0.20 nmol /g) and kidney (0.65 nmol/g). the micronutrient status among school children.
Discussion and Conclusion: The used Spinach in our study Materials and methods: The study is a longitudinal,
contained a high amount of Cd. This amount significantly interventional double-blind and placebo controlled concerning
increased the concentration of liver and kidney MDA. children living in rural areas of Morocco. Micronutrient status
Conversely, GTD completely counteracted the effect of Cd and anthropometric measurements were assessed in 200 children
spinach on the increased hepatic and renal MDA and improved aged 7 to 9 years, before and after intervention. Children were
in parallel the total antioxidant status. divided to two groups that consumed 200 ml of either fortified
milk with (iron, iodine vitamin A and D3) to cover 30% of RDI
CO-06-003 or non fortified milk, over a 9-mo period. Morbidity, alimentary
GENETIC POLYMORPHISM OF CD36, FAT (food frequency questionnaire and 24h food recall) and
socioeconomic surveys were performed at baseline.
TASTE RECEPTOR, IS ASSOCIATED WITH Results: Both groups were comparable at baseline for socio-
DECREASED PREFERENCE OF DIETARY economic status variables, micronutrient status markers and
LIPIDS IN YOUNG OBESE CHILDREN FROM anthropometry measures. At endline intervention group showed:
CONSTANTIN REGION 18% reduction of stunting, elimination of vitamin A deficiency
Amira SAYED1, Jiri PESNIK2, Hadjer DAOUDI1, Abdelkader (from 50% to 4.3%), reduction of vitamin D3 deficiency (from
ROUABAH1, Leila ROUABAH1, Naim A. KHAN2 66% to 28%). reduction of iron deficiency (from 50.9% to
1
Laborartoire de Biologie Cellulaire & Moléculaire, Université 37.2%) and reduction of iodine deficiency (from 72% to 28%).
de Constantine1, Algeria, 2Laboratoire de la Nutrition & Conclusion: These results are a great asset to the National
Toxicologie, UMR U866 INSERM, Dijon 21000, France Nutrition Strategy 2011-2019 especially as they pertain to the
Introduction: Obesity is increasing all over the world, and fat food fortification component.
overconsumption is one of the factors that directly influences this
pathology. Recent studies have suggested the implication of a CO-06-005
common variant of fat taste receptor CD36 (rs1761667-A allele) LIFESTYLE CHANGES AND ANTIOXIDANT
in obesity. The objective was to assess fatty acid sensitivity in ENRICHMENT: A NEW APPROACH TO
relation to CD36 SNP (single nucleotide polymorphism) in
young lean and obese children. PREVENT TYPE 2 DIABETES IN ANIMALS
Materials and Methods: We studied lingual detection Stéphanie DAL, Remmelt VAN DER WERF1, Catherine
thresholds for oleic acid in Algerian children (n=116, age=8±0.5 WALTER1, William BIETIGER1, Elodie SEYFRITZ, Carole
years) in two groups: obese [n=57; BMI z-score=2.513±0.490)] MURA1, Claude PERONET1, Julie LEGRANDOIS2, Dalal
and lean children [n=59; BMI z-score = -0.138±0.601)] by WERNER2, Saïd ENNAHAR3, Fabien DIGEL4, Michel
alternative-forced choice (AFC) method. The children were PINGET5, Nathalie JEANDIDIER5, Eric MARCHIONI3,
genotyped for A/G SNP rs1761667 in 5’UTR region of CD36 by Séverine SIGRIST1
1
using PCR–RFLP. Centre Européen d’Etude du Diabète (CEED), Strasbourg,
Results: We noticed high CD36 A-allele frequency (p=0.036) in France et Equipe de Chimie Analytique des Molécules
young obese children. CD36 A-allele was associated with high BioActives, IPHC-LC4, UMR 7178, Faculté de Pharmacie,
lipid taste perception thresholds than G-allele in obese children. Ilkirch, 2Aérial, Illkirch, France, 3Equipe de Chimie Analytique
Waist circumference was positively correlated with reduced fat des Molécules BioActives, IPHC-LC4, UMR 7178,
4
taste sensitivity in these children. Interprofession des Fruits et Légumes d’Alsace (IFLA), Sainte
Discussion/conclusion: CD36 SNP A-allele, being present both Croix en Plaine, 5Service d’Endocrinologie, Diabète, Maladies
in young lean and obese children, is associated with high Métaboliques, Hôpitaux Universitaires de Strasbourg, France.
threshold for fatty acid taste sensitivity only in obese children. Introduction: Oxidative stress (OS) plays a major in the
pathophysiology of type 2 diabetes and today is a new
therapeutic target for the use of natural antioxidant. Our previous
CO-06-004 studies, combining chemistry and biology, highlighted the
IMPACT OF CONSUMPTION OF MILK important antioxidant activities of red cabbage and cherry among
FORTIFIED IN VITAMINS AND MINERALS other fruits and vegetables. Our aim was to determine in vivo
ON THE NUTRITIONAL STATUS OF SCHOOL their effects on the evolution of diabetes.
CHILDREN IN MOROCCO Methods: After two months of high-fat high-fructose (HFHF)
Fatim Zahra ZAHROU1, Amjed ACHOUR2, Imane EL diet male Wistar rats were divided into: 1) HFHF, 2) standard
MENCHAWY1, Kaoutar BENJED1, MEHDI AZLAF, Asmaa diet ND (lifestyle and dietary measures), 3) ND enriched in red
EL HAMDOUCHI1, Khalid ELKARI1, Hakim BELGHITI3, EL cabbage and 4) in cherry (10%) during two months.
Arbi RJIMATI4, Noureddine EL HALOUI1, Hassan Anthropomorphic (weight, leptine), metabolic (blood glucose, c-
AGUENAOU peptid), plasmatic oxidative parameters (lipid peroxidation) were
1
Unité Mixte de Recherche en Nutrition et Alimentation; quantified. Tissues (liver, pancreas, muscle and vessels) OS were
URAC39 (CNESTEN, Université Ibn Tofaïl). Rabat-Kénitra. assessed by the probe dihydroethidine. Hepatic complications
Morocco, 2Fondation pour la nutrition de l’enfant, 3Hopital (steatosis, fibrosis) and vascular (endothelial dysfunction) were
Militaire d'Instruction Mohammed V, Rabat, 4Mininistère de la determined.

16
Results: The pursuit of HFHF diet worsens diabetes (obesity, cancer agent. This effect may be attributed to its high content of
glucose intolerance, hyperinsulinemia, fasting hyperglycemia), polyphenols, especially oleuropein and hydroxytyrosol.
its complications (hepatic, vascular) and global OS. Dietary
measures with ND and ND cherry improved anthropomorphic
but hyperinsulinemia, tisular OS and endothelial dysfunction Exercise
persist. Only ND red cabbage is able to decrease to physiological
levels all parameters. CO-05-001
Conclusion: These results demonstrate that lifestyle changes are ACUTE EXERCISE PRECONDITIONING
necessary but not sufficient in preventing diabetes. Red cabbage PROTECT MITOCHONDRIAL FUNCTION
improves these benefits. In contrast, consumption of a high
glycemic index antioxidant may be harmful. Thus, the addition AGAINST SKELETAL MUSCLE ISCHEMIA–
of antioxidants to the foods lifestyle modifications should be REPERFUSION
targeted. Anna-Isabel SCHLAGOWSKI, François SINGH, Anne-Laure
CHARLES, Fabrice FAVRET, François PIQUARD, Bernard
CO-06-006 GENY, Joffrey ZOLL
EA3072, Fédération de Médecine Translationnelle, Institut de
PHENOLIC EXTRACTS OF OLEASTER Physiologie, Université de Strasbourg, 67000 Strasbourg,
(OLEA EUROPEA L) LEAVES INDUCE France
APOPTOSIS IN COLON-CANCER CELLS VIA Introduction. Ischemia-reperfusion (I-R) induces mitochondrial
THE MITOCHONDRIAL APOPTOTIC function impairments and oxidative stress in skeletal muscle. The
PATHWAY objective was to show that a single exercise (EXO) prior to the
Wafa ZERIOUH, Meriem BELARBI1, Aurélie FLUCKIGER2, I-R period protects the hind limb mitochondrial function.
Charles THOMAS3, Chahid BENAMMAR4, Mohammed Materials and methods: 20 mice were divided into 2 groups:
choukri BEGHDAD5, Naim Akhtar KHAN6, Lionel APETOH7, The control group (CTL I-R, n=10) underwent I-R without
Mickael RIALLAND8, Francois GHIRINGHELLI9, Aziz exercise and the exercise group (EXO I-R, n=10) ran before I-R.
HICHAMI10 Mice underwent 2 hours of ischemia induced by a rubber band
1
Research Laboratory "Natural Products" Faculty of SNV-STU, tourniquet applied on the right root of the hind limb (the left leg
Abou-Bekr Belkaïd, Tlemcen - ALGERIA, 2INSERM, U866, was used as control leg), followed by a reperfusion period of 2 h.
Dijon - FRANCE, 3INSERM, U866, Dijon - FRANCE, 4 Research The EXO was performed on a treadmill 1h before I-R.
Laboratory "Natural Products" Faculty of SNV-STU, Abou-Bekr Results: Blood lactate obtained at the end of EXO was above 9
Belkaïd, Tlemcen - ALGERIA,, 5Research Laboratory "Natural mmol/L. In skinned gastrocnemius (GAS) fibers of CTL mice, I-
Products" Faculty of SNV-STU, Abou-Bekr Belkaïd, Tlemcen - R decreased the maximal mitochondrial respiration (Vmax) in
ALGERIA,, 6INSERM, U866, Dijon - FRANCE, 7INSERM, comparison to the control leg (23.6 vs 28.6 pmol/(sec*mg wet
U866, Dijon - FRANCE, 8INSERM, U866, Dijon - FRANCE, weight); p<0.05). In EXO mice, GAS Vmax was increased in
9
INSERM, U866, Dijon - FRANCE, 10INSERM, U866, Dijon, both the ischemic and the control legs (39.5 and 31.8
FRANCE. pmol/(sec*dw respectively p<0.05). In EXO mice, the GAS
Introduction: The oleaster (Olea europea L.) leaves have been Vmax impairment was reduced after I-R (p=0.22). In CTL mice,
traditionally used in the cancer treatment. Colorectal cancer is I-R increased muscle H202 production (42.6 vs 37.8 µmol/mg
the second leading cause of cancer deaths in both men and dw; p=0.23). In EXO mice, the H202 production was reduced in
women around the world. In this study we investigated the the I-R leg in comparison of the I-R leg of CTL mice (26.6 vs
mechanisms by which Phenolic Extracts of the Oleaster leaves 42.6 umol/mg dw in CTL mice; p<0.01).
(PEOL) induced apoptosis of colon cancer cell lines and CT26 Conclusion: These results showed that a preconditioning
tumor growth. exercise protect the muscle mitochondrial function from a period
Materials and Methods: The Human Colon Cancer Cells of I-R.
(HCT-116, HCT-8) and mouse colon carcinoma cell (CT-26)
were treated with PEOL at the concentration of 0, 5, 10, 20, 30,
50 µg/ml for 24h. Cleavage of caspase-9 and poly (ADPribose) CO-05-002
polymerase (PARP) was evaluated by western blot and BDNF AND CHRONIC CEREBRAL
mitochondrial membrane potential was measured by using HYPOPERFUSION IN RATS. EFFECTS OF
TMRM as fluorescent probe. BALB/c mice were subcutaneously EXERCISE
implanted with CT26, then infusion of Oleaster leaves (0.1%) Hayat BANOUJAAFAR, Alice MONNIER, Claude MOSSIAT,
was given in the feeders. Anne TESSIER, Christine MARIE
Results: Trypan Blue assays showed that PEOL dose- INSERM U1093 Cognition, Action et Plasticité Sensorimotrice,
dependently reduced the viability of all cancer cell lines in vitro. Dijon.
Western blot analysis of cell lysates from HCT-116 and HCT-8 Introduction: Chronic cerebral hypoperfusion is associated with
revealed that PEOL induced the cleavage of both PARP and cognitive deficit that has been related to decreased nitric oxide
caspase-9, the latter is a critical marker of the intrinsic (NO) production. While brain-derived neurotrophic factor
mitochondrial pathway for apoptosis. Hence, the TMRM use (BDNF) is largely involved in cognition and in the procognitive
confirmed that PEOL decreased themitochondrial membrane effect of physical exercise (EXE), studies on the effect of chronic
potential. Furthermore, oleaster leaves infusion significantly cerebral hypoperfusion alone or in combination with EXE on
reduced CT26 tumor growth in the mice strain. brain BDNF levels are lacking.
Discussion/conclusion: These results demonstrate that Oleaster Materials and Methods: BDNF levels and the phosphorylated
leaves have a strong potential for development as an anti-colon
17
(ser1177) form of endothelial NO synthase (P-eNOS) were CO-05-005
measured in the cortex and hippocampus using Western blot INFLUENCE OF VO2 FLUCTUATIONS ON
analysis in 4 groups of rats (n=6 each): 1) rats subjected to
bilateral common carotid artery occlusion as a model of chronic AMPK, P38-MAPK AND CAMKII
cerebral hypoperfusion (BCCO rats), 2) sham rats, 3) BCCO rats SIGNALLING IN HUMAN SKELETAL
subjected to EXE (a treadmill walking activity at 18m/min, MUSCLE
30min/j for 7 days), 4) sham rats subjected to EXE. This Adrien COMBES1, Jeanne DEKERLE2, Nick WEBBORN3,
modality of EXE increases P-eNOS levels in the microvascular Peter WATT, Valérie BOUGAULT4, Frédéric DAUSSIN
1
fraction isolated from the cortex of control rats. Université de Lille, 2University of Brighton, 3University of
Results: As compared to sham rats, BCCO rats exhibited Brighton, 4Université de Lille, France.
decreased BDNF and P-eNOS levels in the cortex and Introduction: Skeletal muscle contraction increases
hippocampus. In these regions, EXE increased BDNF levels in intracellular ATP turnover, calcium flux and mechanical stress
sham rats but not in BCCO rats, while it did not modify P-eNOS initiating signal transduction pathways that modulate
levels. transcriptional programs. The purpose of this study was to
Discussion/conclusion: Our results support the contribution of determine if the metabolic disturbances per se regulate signalling
cerebral BDNF loss to cognitive deficit induced by chronic cascades know to regulate peroxisome proliferator-activated
cerebral hypoperfusion and show the failure of EXE to elevate receptor coactivator-1 (PGC-1).
brain BDNF levels in the hypoperfused brain. They also question Materials and Methods: Nine males performed a continuous
the sensitivity of the measurement of P-eNOS levels in brain (30min) and an intermittent (30 times: 1min of exercise-1min of
tissue to assess NO production by endothelium. rest) exercises at 70% of VO2peak on two separate occasions.
Skeletal muscle biopsies form the vastus lateralis were taken at
CO-05-004 rest and at +0h and +3h after exercise.
Results: VO2 response analysis reveals a 3.3-fold higher
HOW DO DIFFERENT LEVELS OF ACUTE metabolic fluctuations after intermittent exercise despite an
HYPOXIA ALTER RUNNING KINETICS AND identical energy expenditure (317 ± 41 vs. 312 ± 56 kJ after
KINEMATICS DURING REPEATED SPRINTS? intermittent and continuous exercise, respectively). AMP-
F. BROCHERIE, G.P. MILLET1, J.B. MORIN2, O. GIRARD3 activated protein kinase (AMPK) (~2.9-fold, P < 0.01),
1
ISSUL, Institute of Sport Sciences, Department of Physiology, calcium/calmodulin-dependent protein kinase II (CaMKII)
Faculty of Biology and Medicine, University of Lausanne, (~2,7, P < 0.01) and p38 mitogen-activated protein kinase
2
Laboratory of Human Motricity, Education Sport and Health, (MAPK) (~4,2, P < 0.01) phosphorylation increased
University of Nice Sophia Antipolis, 3 ISSUL, Institute of Sport immediately after intermittent exercise in a greater extent
Sciences, Department of Physiology, Faculty of Biology and compared to continuous exercise (condition-by-time interaction,
Medicine, University of Lausanne p>0.05).
Introduction: We examined the effects of different levels of Discussion/conclusion: The metabolic disturbances induced by
altitude on running mechanics alterations during repeated intermittent exercise regulate the activation of multiple signaling
treadmill sprinting. pathways in response to a single bout of exercise. Further work
Materials and Methods: Thirteen recreational team-sport is required to determine if the marked difference in signaling
athletes performed eight 5-s sprints with 25-s of passive recovery pathways activation during the present protocol would be
on an instrumented treadmill, allowing the continuous manifest as divergent increases in mitochondrial content after a
measurement of running kinetics and kinematics. These were period of exercise training with the respective modalities.
randomly conducted in normoxia (SL; sea-level), moderate
(MH; FiO2 = 16.8% / simulated altitude ~1800 m) and severe CO-05-006
normobaric hypoxia (SH; FiO2 = 13.3%~3600 m).
Results: First sprint distance was similar (P>0.05) in all REDUCED EXERCISE CAPACITY IN
conditions. Compared to SL (-5.3±1.9% and 183.2±9.3 m), PATIENTS WITH FIBROMYALGIA:
larger (P<0.05) sprint decrement score and lower (P<0.05) CENTRAL OR PERIPHERAL MECHANISMS?
cumulated distance covered over the eight sprints occurred in SH Maryse HENGEN, Evelyne LONSDORFER-WOLF, Jamal
(-8.2±3.9% and 178.5±10.7 m) but not in MH (-7.2±3.5% and BOUITBIR, Anne Laure CHARLES, Julien MASAT, Marie-
181.4±10.3 m).Mean vertical, horizontal and resultant ground Eve ISNER, Jehan LECOCQ, Philippe CLAVERT, Joffrey
reaction forces decreased from the first to the last repetition in all ZOLL, Bernard GENY
conditions (compounded values: -2.3, -8.6 and -2.4%). Averaged Mitochondrie, stress oxidant et protection musculaire, FMTS,
horizontal forces for the eight sprints were -4.9% and -5.2% E.A. 3072, University of Strasbourg, Strasbourg, France
lower (P<0.05) in SL and MH versus SH. Contact, flight and Introduction. Fibromyalgia is a common disease responsible for
swing times increased with fatigue (compounded values: +12.7, widespread musculoskeletal pain. The aim of this study was to
+4.2 and +8.2%), while stride length and frequency decreased determine exercise capacity in patients with fibromyalgia (FM),
(compounded values: -8.3 and -2.5%). Averaged contact times and eventual central (cardiorespiratory) or peripheral (skeletal
for the eight sprints were 4.0 and 3.3% longer and stride muscle mitochondrial dysfunctions) limitation factors.
frequencies were both 2.3% lower in SL and MH versus SH. Methods. We studied clinical and biological data, hemodynamic
Conclusion: At a simulated altitude of ~3600 m, impairments in parameters, spirometry, submaximal (6MWT) and maximal
repeated-sprint ability and the magnitude of fatigue-induced (maximal cardiopulmonary bicycle testing) exercise capacity in
kinetics and kinematics alterations exceed those observed near 24 FM patients and compared them to reference values.
sea level or at ~1800 m. Mitochondrial respiration of FM patients' left deltoid muscles
were also determined using glutamate-malate (Vmax; complexes
18
I, II and IV activities), succinate (Vsucc; complexes II, III and JUDOKAS
IV activities) and TMPD-ascorbate (VTMPD/Asc. complexe IV Hamdi CHTOUROU1, Nizar SOUISSI2, Anis CHAOUACHI3
activity), respectively. Oxidative stress was determined by 1
High Institute of Sport and Physical Education, Sfax, Sfax
measuring mitochondrial H2O2 production. Results were University, Tunisia, 2Research Laboratory ''Sports performance
compared to those of 4 control subjects. optimization'' National Center of Medicine and Science in Sports
Results. Biological values, hemodynamic parameters and (CNMSS), Tunis, Tunisia, 3Research Laboratory ''Sports
spirometry were normal. 6MWT and maximal cardiopulmonary performance optimization'' National Center of Medicine and
bicycle testing showed reduced exercise capacity in FM patients, Science in Sports (CNMSS), Tunis, Tunisia
as compared to references values. Patients walked a mean Introduction: Sleep loss is observed in many situations for
distance of 413 ± 22 m, significantly (p < 0.0001) lower than the athletes (e.g., jetlag, etc.). However, data concerning the effect
mean theoretical distance (587 ± 15 m). Mean peak VO2 was of partial sleep loss on muscle performance and fatigue in highly
18.8 ± 1.2 ml/min/kg, significantly lower (p = 0.0073) than the trained athletes present inconclusive findings. Therefore, we
theoretical value of 24.1 ± 1.4. Mitochondrial Vmax (-38%, aimed to investigate the effect of partial sleep deprivation on
p=0.004) and VTMPD/asc (-46%, p<0.0001) were significantly muscle fatigue and short-term maximal performances of judo
reduced in FM patients. H2O2 production tended to be increased athletes.
in FM patients. Materials and Methods: Thirteen judokas completed a Wingate
Conclusions. Exercise capacity is impaired in FM patients. test before and after a simulated judo match at 16:00 h following
These data suggest that peripheral factors such as impaired a reference-normal sleep night condition (RN) and a sleep
skeletal muscle mitochondrial function might play a role. deprivation at the beginning of the night (SDB) condition.
Lactate concentrations [La] was measured before and 3-minutes
Sleep after the match. Perceived exertion (RPE) was measured after the
combat.
Results: During the Wingate test, muscle power was
CO-07-001 significantly reduced and fatigue index increased significantly
SLEEP LOSS EFFECTS ON INTERLEUKIN-6 after SDB in comparison with RN after the judo match. After the
DURING EXERCISE combat, RPE scores were significantly higher after SDB than
Nizar SOUISSI1, Salma ABEDELMALEK, Hamdi RN. [La] was significantly higher after RN in comparison with
CHTOUROU2, Anis CHAOUACHI SDB. However, before the combat there was no significant
1
Research Laboratory ‘‘Sports Performance Optimization’’ difference between SDB and RN.
National Centre of Medicine and Science in Sports (CNMSS), Discussion/conclusion: After the combat, performance and
Tunis, Tunisia, 2High Institute of Sport and Physical Education, fatigue during the Wingate test were significantly affected by
Sfax, Sfax University, Tunisia sleep loss. This result was accompanied by a higher subjective
Introduction: The disruption of the sleep-wakefulness cycle has perception of fatigue. Therefore, judokas may present a worse
consequences on immune functions (i.e., Interleukin-6 (IL-6)) performance after sleep loss. In contrast, we observed a lower
and sport performance. The aim of the present study was to [La] after SDB in comparison with RN. This result could be
examine the effect of partial sleep deprivation (PSD) on physical explained by the lower effort realized during RN in comparison
performance and Interleukin-6 (IL-6). with SDB.
Materials and Methods: Twelve soccer players performed the
Wingate test in the afternoon (i) a reference-normal-sleep-night
(RN) and (ii) a 4-h of PSD at the end of the night. Plasma IL-6
Anesthesia
concentrations were measured before (T1), immediately after
(T2), and 60 min after the exercise (T3). Invited lecture
Results: We showed that muscle power (i.e., peak and mean SEPTIC SHOCK RESUSCITATION: TIME
power) during the Wingate test were altered by the PSD FOR A NEW PARADIGM
condition (p<0.05). In both condition (i.e., RN and PSD) IL-6 Julien POTTECHER, Olivier COLLANGE
increased from T1 to T2 and T3 (p<0.05). IL-6 was significantly Réanimation Chirurgicale, Service d'Anesthésie-Réanimation
higher during PSD than RN at T3. However, there was no Chirurgicale, Hôpital de Hautepierre, Hôpitaux Universitaires
significant difference between PSD and RN at T1 and T2. de Strasbourg, 1 Avenue Molière, 67098 Strasbourg.
Discussion/conclusion: The present study’ findings Recently, the PROMISE and ARISE investigators demonstrated
demonstrated that the Wingate test my increase the IL-6 that Early Goal-Directed Therapy (EGDT) failed to decrease
concentrations. This increase may reveal its role in initiating mortality, as compared with usual care, among patients with
biochemical signalling pathways in skeletal muscle, and early septic shock. Confirming that strict adherence to
regulating metabolism in healthy individuals, especially in hemodynamic endpoints did not translate into improved survival,
sportsmen. Likewise, we showed that IL-6 increased after PSD these data seriously question our therapeutic paradigm in septic
during the recovery phase. The higher IL-6 concentrations after shock resuscitation. Thus, acknowledging macro- and
PSD could be attributed to a higher muscle fatigue. In agreement, microcirculatory improvements by EGDT, further hemodynamic
the fatigue index during the Wingate test was significantly higher therapy and oxygen transport increase will not prove beneficial
after PSD in comparison with after RN. if oxygen reaching cells cannot be used by mitochondria for ATP
synthesis. Indeed, sepsis is characterized by impaired
CO-07-002 mitochondrial respiratory chain complexes activity, increased
SLEEP LOSS: EFFECTS ON PHYSICAL mitochondrial oxidative stress and/or early mitochondrial
transition pore opening. Skeletal muscle mitochondrial
PERFORMANCE AND MUSCLE FATIGUE OF
19
dysfunction has been associated with the severity and outcome SCHNEIDER2, Pierre DIEMUNSCH3, Bernard GENY4, Julien
of septic shock and inhibition of mitochondrial permeability POTTECHER5
1
transition improved cardiac function and reduced mortality EA 3072, FMTS, Faculté de Médecine, Université de
during sepsis. Without neglecting early hemodynamic Strasbourg, 2EA 3072, FMTS, Faculté de Médecine, Université
optimization, new therapeutic approach should target de Strasbourg, 3EA 3072, FMTS, Faculté de Médecine,
mitochondria, protecting them from injury and/or enhancing Université de Strasbourg, 4EA 3072, FMTS, Faculté de
their recovery in order to reduce cytopathic hypoxia, and Médeince, Université de Strasbourg, France , 5EA 3072, FMTS,
therefore sepsis-induced multi-organ failure. Faculté de Médecine, Université de Strasbourg, France
Introduction: Prone position (PP) surgery under general
CO-08-001 anesthesia (GA) frequently leads to arterial hypotension.
ASSOCIATION BETWEEN TRANSPUL- Vasopressors and/or fluid expansion are empirically used to treat
this hemodynamic instability with inconstant results. The aim of
MONARY GRADIENTS OF REACTIVE this study was to elucidate mechanisms underlying this
OXYGEN SPECIES, PULMONARY instability in order to improve its management.
VASCULAR RESISTANCES AND ARTERIAL Materials and Methods: After IRB approval (NCT01957605)
OXYGENATION IN HIGH-RISK and signed informed consent, patients scheduled for major
CARDIOSURGICAL PATIENTS neurosurgery in prone position were equipped with a calibrated,
Pamela KHALIFEH, Luc FENNINGER1, Adrien THIBAUT2, continuous cardiac output monitoring (PiCCO2®, Pulsion
Mickael SCHAEFFER3, Paul Michel MERTES4, Julien Medical Systems) Mean systemic filling pressure and resistance
POTTECHER5 to venous return (RVR) were estimated by building venous
1
Department of Critical Care, Haguenau Hospital, 2 Department return curves as recently described by Pinsky et al. Airway and
of Anesthesiology and Critical Care - Strasbourg University intra-abdominal (vesical) pressure were also recorded. Data were
Hospital , 3 Public Health Department - Strasbourg University collected after induction of GA in the supine position and after
Hospital, 4Department of Anesthesiology and Critical Care - moving the patient in PP.
Strasbourg University Hospital, Strasbourg. Results: Nine consecutive patients were included. Indexed RVR
Introduction: High-risk cardiac surgical patients often develop increased (676 ± 236 vs 955 ± 432 dyne.s/cm5/m2, p<0.05)
acute respiratory failure after open-heart surgery under without significant cardiac index changes. Dynamic index of
cardiopulmonary bypass. The pathophysiologic substratum for preload-dependence significantly increased as did intra-
arterial hypoxemia is imperfectly understood but may imply abdominal pressure (6±3 vs. 13±3 mmHg, p<0.01). Airway
intrapulmonary oxidative stress and increased venous pulmonary pressures were not altered in a clinically relevant extend.
vascular resistances (RVeP). Discussion: Using an original approach we confirmed deep
Materials and Methods: After IRB approval and informed alterations in the venous return in the PP. Despite no significant
consent, we took advantage of both pulmonary arterial and left change in cardiac index, PP led to a state of preload-dependence,
atrial catheters in high-risk surgical patients (Kor score > 22) to along with increased resistances to venous return, mainly
investigate transpulmonary gradients of vascular resistances and localized at the abdominal level. Confirmation of these results in
reactive oxygen species production and their relation with a larger scale series may lead to modify patient positioning in
arterial oxygenation (alveoloarterial oxygen difference, order to better avoid abdominal compression during PP.
AaDO2). Repeated measures were carried out pre and post-
operatively and statistical analysis run under the Bayesian CO-08-003
paradigm using linear mixed models. MICE SURVIVAL IN A TWO HIT MODEL OF
Results: Seventeen patients were enrolled. AaDO2 was SEPSIS DEPENDS ON INTRATRACHEAL
associated with the capillary-left atrial pressure gradient, PSEUDOMONAS AERUGINOSA BACTERIAL
(coefficient value: 0.49; 95%CI [0.04-0.95] Pr(coef>0)=0.98),
with RVeP, (coefficient value: 0.019; 95%CI [-0.0005-0.0377], LOAD.
Pr(coef>0)=0.97) and was non-significantly associated with Damien RESTAGNO, Jeanne-Marie BONNET1, Angeli
transpulmonary reactive oxygen species gradient, (coefficient KODJO1, Fabienne VENET3, Christian PAQUET1, Ludovic
value -6.9; 95%CI [-17.9-4.31], Pr(coef>0)=0.11) FREYBURGER1, Vanessa LOUZIER1
1
Discussion: Even if the small sample size precludes any Vetagro-sup, 2Vetagro-sup, 3Groupement hospitalier Edouard
definitive conclusion, postoperative hypoxemia in high-risk Herriot, Laboratoire d'immunologie cellulaire,
cardiosurgical patients after cardiopulmonary bypass may be Introduction: Sepsis is a systemic reaction in presence of an
associated with pulmonary venous constriction and infection characterized by an early systemic inflammatory
intrapulmonary reactive oxygen species production. response syndrome (SIRS) followed by a compensatory anti-
inflammatory response syndrome (CARS). The first side of this
typical immune response is responsible for widespread organ
damage whereas the second part leads to an immunoparalysis
CO-08-002 increasing patients’ susceptibility to secondary infections. We
HEMODYNAMIC CHANGES DURING PRONE aim to finalize a murine model to mimic and understand sepsis
POSITION SURGERY: NEW INSIGHTS ON physiopathology.
VENOUS RETURN GAINED FROM Materials and methods: Sepsis is induced by mild CLP. Blood
ESTIMATION OF MEAN SYSTEMIC FILLING is collected 2h, 6h, 1, 2, 3, 5 and 13 days after CLP to quantify
plasmatic TNF?, IL-6, IL-10.At day 5, splenocytes are collected
PRESSURE AND VENOUS RESISTANCES and used for immunological assays or mice are intratracheally
Benjamin LEBAS, Thien-Nga CHAMARAUX-TRAN1, Francis instilled with Pseudomonas aeruginosa (5.106, 2.107 and 108
20
CFU) to evaluate survival. INCREASES EARLY DURING SEPTIC SHOCK
Results: TNF, IL-6 and IL-10 increase 2h after CLP and remain Raphaël CLERE-JEHL, Julie BOISRAME1, Anne-Laure
high for the whole experiment, as compared to Sham.At day 5, CHARLES2, Ferhat MEZIANI3, Joffrey ZOLL2, Bernard
for CLP mice, whereas total T cells population (CD3+) GENY2, Pascal BILBAULT2
decreases, Treg cells fraction (CD4+/CD25+) increases. In 1
Service de réanimation médicale, Nouvel Hôpital Civil, CHRU
parallel, T cells proliferation diminishes. LPS-stimulated de Strasbourg, 2Equipe d’accueil 3072, Fédération de Médecine
splenocytes ability to release TNF also decreases. Survival is Translationnelle, Institut de Physiologie, Université de
100% after 5.106 CFU, 50% for CLP mice after 2.107 CFU and Strasbourg, 3Service de réanimation médicale, Nouvel Hôpital
0% for CLP and Sham after 108 CFU. 2 days after instillation Civil, CHRU de Strasbourg, France.
(2.107 CFU), Pseudomonas is detected in CLP and Sham’s lungs Introduction: To further understand the mechanisms leading to
but only in CLP mice’s spleen and liver. Compensatory Anti-inflammatory Response Syndrome (CARS)
Discussion/Conclusion:This study demonstrates that following septic shock, we studied circulating lymphocytes and
immunosuppression following CLP increases mice monocytes mitochondrial respiration during 7 days following
susceptibility to secondary Pseudomonas aeruginosa septic shock.
intratracheal infection. This susceptibility depends on bacterial Methods: We included Intensive Care Unit (ICU) patients
load. diagnosed for septic shock less than 24 hours earlier, using
Surviving Sepsis Campaign criteria. After separating
CO-08-004 lymphocytes and monocytes with Ficoll density gradient
MITOCHONDRIAL OXIDATIVE CAPACITY medium, we measured their O2 consumption, using high
DURING ANAPHYLACTIC SHOCK IN resolution oxygraphy, at day 1, 2 and 7 after sepsis and compared
to same measurements performed in healthy volunteers. Only
SENSITIZED-RATS, A PRELIMINARY STUDY one sample was performed for healthy subjects, who were
Walid OULEHRI, Olivier COLLANGE, Feng ZHENG, Charles supposed to have a stable O2 consumption. We also measured
TACQUARD, Anne-Laure CHARLES, Joffrey ZOLL, Bernard production of superoxyde O 2-. Using Electron Paramagnetic
GENY, Paul-Michel MERTES Resonance.
Department of Anesthesiology, Zhongnan Hospital of Wuhan Results: Lympho-monocytes from septic patients exhibited
University, Wuhan increased O2 consumption, (8.18 ± 2.77.9.50 ± 1.60 and 10.72 ±
Introduction: The pathophysiology of anaphylactic shock is 2.34 versus 4.56±1.29 pmol/s/millions, (p<0.01) at days 1, 2 and
incompletely characterized. It is usually described as distributive 7 after sepsis as compared to healthy lympho-monocytes. There
by analogy with septic shock (anaerobic metabolism, high tissue was no significant difference regarding plasma pH or production
oxygen pressure). However, we already showed that of superoxyde O2-..
anaphylactic shock was associated with an acute heart failure and Conclusion: increased lympho-monocytes mitochondrial
a sharp decrease in skeletal tissue oxygen pressure. This respiration at early stage of septic shock suggests a compensatory
paradoxical oxygen peripheral overconsumption could be the response to sepsis injury. Whether this is related to increased
consequence of sustained mitochondria function. However, there mitochondrial biogenesis and an anti-inflammatory response
is no data describing mitochondrial oxidative capacity during deserves further studies.
anaphylactic shock. The aim of this study was to assess the
mitochondrial oxidative capacity during anaphylactic shock.
Materials and methods: Ovalbumin-sensitized anaphylactic CO-08-006
shock rats (n=7) were compared to control rats (n=7) for REVERSIBLE PERIPORTAL MUSCULAR
systemic hemodynamics. Mitochondrial oxidative capacity was MITOCHONDRIAL RESPIRATORY RATE
assessed using permeabilized fibers (gastrocnemius and soleus IMPAIRMENT INDUCED BY LAPAROSCOPIC
skeletal muscles and heart left ventricle) or isolated mitochondria SURGERY
(brain, lung, liver). Reactive species formation (ROS) and H 2O2 Anne-Laure CHARLES1, Eric NOLL, Michele DIANA2, Yu-
release were also assessed (skeletal and heart muscles). Yin LIU3, Seong-Ho KONG4, Joeffrey ZOLL5, Pierre
Results: The ovalbumin group showed an early and profound DIEMUNSCH6, Bernard GENY7
arterial hypotension, as previously described. Mitochondrial 1
Laboratoire de physiologie E.A. 3072, 2Institut Hospitalo-
oxidative capacities were not altered in the liver, the lung, the Universitaire de Strasbourg, 3Institut Hospitalo-Universitaire de
brain and in the soleus. Maximal mitochondrial oxidative Strasbourg, 4Institut Hospitalo-Universitaire de Strasbourg,
capacities significantly decreased in the heart (-36%, 399±131 5
Laboratoire de Physiologie E.A 3072, 6Laboratoire de
vs. 144±33 O2 µmol/min/mg, p =0.04) and increased in the Physiologie E.A 3072, 7Laboratoire de Physiologie E.A 3072,
gastrocnemius (+24%, 99±55 vs. 173±45 O2 µmol/min/mg, France.
p=0.03). There was no significant difference in terms of ROS Introduction: Surgical incisions are a major source of
formation and H2O2 release. postoperative pain and complications such as hernias and
Discussion/conclusion: In our model of anaphylactic shock, infections. In minimally-invasive surgery (MIS), wound
mitochondrial oxidative capacity was not altered in most of the infiltration with local anesthetics (LA) is a recommended
organs studied. However, heart mitochondria were significantly practice in the framework of enhanced postoperative recovery
altered when gastrocnemius mitochondria were significantly programs. In this study, we aimed to isolate the effect of
over revving. laparoscopic procedures on the peri-portal muscular
mitochondrial respiratory chain (MRC).
CO-08-005 Material and methods: After institutional and national ethical
MITOCHONDRIAL RESPIRATION OF committee approval, 6 large white swine underwent a 4-port
HUMAN LYMPHOCYTES AND MONOCYTES laparoscopic sigmoid resection. Ropivacaine 7.5 mg/ml at 1.4
21
mg/kg per sites was injected into the abdominal wall before junctions and on transporter levels. These mechanisms will be
trocars insertion. Rectus abdominis muscle were surgically investigated in a future study.
sampled at the port insertion site, before ropivacaine injection P-02-002
(BL), 3 hours after port insertion (H3) and 10 days (D10) after DEVELOPMENT OF AUDITORY BINAURAL
the surgical procedures. MRC function was assessed using
oxygraphy.Analysis of variance (ANOVA) followed by the INTERACTIONS IN RAT SUPERIOR
Bonferroni multiple comparison test was performed. COLLICULUS
Results: Basal respiratory state (V0) and respiratory rates with Jean Paul GUILLEMOT
saturing amount of ADP (Vmax) was decreased 3h after port Université du Québec à Montréal, Canada.
insertion compared to baseline (V0: 0.14±0.01 vs 0.10±0.02 Introduction: Auditory neurons of the rat superior colliculus are
micromol O2.min-1.g wet weight-1,Vmax: 0.42±0.04 vs sensitive to the spatial position of a sound and show auditory
0.29±0.04 micromol O2.min-1.g wet weight-1, p<0.05, binaural interactions. However, no study has investigated the
respectively) and were restored 10 days post operative (V0: development of their sensitivity to interaural intensity
0.15±0.01 micromol O2.min-1.g wet weight-1and Vmax: differences or the maturation of the auditory space map which
0.42±0.05 micromol O2.min-1.g wet weight-1, p>0.05 vs BL). they define. The aim of this study was, therefore, to examine the
These results are in favor of a reversible muscular insult during development of interaural intensity differences sensitivity of
trochar insertion and peritoneal pressuring. auditory neurons in the rat superior colliculus.
Materials and Methods: Extracellular unit recordings were
carried out in the intermediate and deep layers of the superior
Thematic Sessions of the SFP colliculus in anaesthetised rats separated into five post-natal age
groups : P15-18, P21-24, P27-30, P36-39 and older than P60.
(Poster presentations) Interaural intensity difference sensitivity was determined during
Neurophysiology closed field dichotic stimulations with gaussian noise bursts.
Results: In all groups, the majority of superior colliculus
auditory neurons showing binaural interactions were classified
P-02-001 as EO/I, that is, they showed an excitatory response to monaural
EFFECTS OF HYPOXIA/NORMOXIA CYCLES stimulation of the contralateral ear and no observable response
ON MEMBRANE INTEGRITY IN RODENT IN during stimulation of the ipsilateral ear. Stimulating both ears
simultaneously evoked inhibitory interactions as sound intensity
VITRO BLOOD BRAIN BARRIER MODEL in the ipsilateral ear increased. Binaural interaction was present
Frédéric ROCHE 1, Nathalie PEREK2, Morgane CHATARD in a low proportion of neurons (17%) at P15-18. The proportion
1
EA 4607 Système Nerveux Autonome – Epidémiologie sensitive to interaural intensity differences increased with age
Physiologie Ingénierie Santé, Université Jean Monnet Saint and the adult values (~90%) were attained at P27-30.
Etienne, COMUE de Lyon, CHU Nord de Saint Etienne, France Conclusion: These results show that three days after hearing
, 2EA 4624 Laboratoire Interdisciplinaire d’études des onset (P12) in the rat, superior colliculus auditory neurons are
Nanoparticules Aérosolisées, Université Jean Monnet Saint sensitive to interaural intensity differences
Etienne, COMUE de Lyon, Faculté de médecine Jacques
Lisfranc de Saint Etienne, France.
Introduction: One possible cause of blood-brain barrier (BBB) P-02-003
disruption could be represented by repeated hypoxia. Several EVALUATION OF THE BENEFICIAL EFFECT
medical disorders are linked to chronic intermittent hypoxia. OF ANISEED AQUEOUS EXTRACT ON
However, the impact of repeated hypoxic stress on in vitro BBB NERVOUS SYSTEM OF INTOXICATED RATS
integrity is still unknown. This study describes a new in vitro
WITH LEAD (PB).
BBB model to investigate the impact of hypoxia/normoxia
Amina BEKARA, Nadia AIT HAMADOUCHE 1, Khaled
cycles on BBB integrity.
KAHLOULA2, Sara HAROUAT3, Dalila TABBAS4,
Materials and Methods: Our BBB model was composed of the
Abdelkader AOUES5
immortalized mouse brain endothelial cells (bEnd.3) which was 1
Laboratory of Biochemistry, University ES-Senia, 3100 Oran
cocultured with the rat malignant glioma cells (C6). It was
(Algeria), 2Laboratory of Biochemistry , Department of Biology
validated by transendothelial electrical resistance (TEER) and
, University of Dr; TAHER MOLAY, 2000 Saida, 3Laboratory of
sodium fluorescein permeability measurements. Hypoxia was
Biochemistry, University ES-Senia, 3100 Oran (Algeria),
induced by 100 µM of hydralazine lasting 2 h then cells were 4
Laboratory of Biochemistry, University ES-Senia, 3100 Oran
exposed to normoxia for 8 h. This cycle was repeated 3
(Algeria), 5Laboratory of Biochemistry, University ES-Senia,
consecutives times. Induction of hypoxia was confirmed by
3100 Oran (Algeria)
studying the expression of HIF-1 with cell-ELISA method. The
Introduction: Lead is a potent neurotoxin agent that causes
impact of hypoxia /normoxia cycles was evaluated on TEER
brain damage and cognitive deficit. The aim of this study was
value and membrane permeability.
to investigate the possible beneficial effect of Aniseed
Results: Our model of contact coculture had the expected
(Pimpinella anisum L ) aqueous extract against earlier
characteristics of an in vitro BBB model. Hypoxia/normoxia
intoxication with this heavy metal.
cycles significantly decreased the TEER value and led to a
Materials and Methods: Pregnant rats were exposed to 0.2% of
significant increase of membrane permeability up to 300 % after
lead acetate during gestation and lactation. The pups received P.
the third cycle.
anisum aqueous extract after weaning.The effect of the extract
Discussion/Conclusion: These data showed that repeated
was evaluated through behavioral test: open filed and forced
hypoxic stress led to a significant increase in membrane
swimming test (FST), and analysis of biochemical parameters:
permeability which could be caused by an alteration of tight
22