Reprod. Nutr. Dev. 46 (2006) 283–338 283c© INRA, EDP Sciences, 2006DOI: 10.1051/rnd:2006012

Session I. Circulation and cellular andmolecular physiology

Physiological cardiac hypertrophy and geneexpression of β adrenergic and M2 mus-carinic receptors. J. Barbier, J. Marchais, F.Rannou-Bekono, F. Carré (Laboratoire de Phy-siologie, Université de Rennes 2, Av. C. Tillon,35044 Rennes Cedex, France).

Endurance training induces cardiovascularadaptations. Alterations in the expression of βadrenoreceptors (β AR) and in M2 muscarinicreceptors (M AchR) have been suggestedto be involved in these processes but theirunderstanding is incomplete. The objective ofthis work was to assess if adaptations linkedto endurance training are associated withmodifications in mRNA abundance and/orprotein levels of different β-AR subtypes andM2 AchR. At the end of an 8 weeks treadmillprotocol, cardiac parameters were evaluated byan electrocardiographic analysis. We measuredβ AR and M2 AchR mRNA level (by real-timeRT-PCR) and protein density (by western blot).A physiological cardiac hypertrophy (+11%),a bradycardia (P < 0.01) and an increaseddiastolic function (P < 0.01) were observed intrained rats. The β3 AR mRNA level remainedunchanged in trained as compared to sedentaryrats; by contrast, the β3 AR protein densityincreased (+54%; P < 0.05). There was nochange in β1 AR mRNA level associated toa non-significant trend towards a decreaseof β1 AR protein level (–26%; P = 0.07)in trained rats. These results also suggest apost-translational regulation of β1 AR andβ3 AR gene expression. For β2 AR and M2

AchR, there was no change neither in mRNAlevel nor in protein density. This study showsthat adrenergic and muscarinic systems aredifferentially regulated following training whenusing results on mRNA and protein expressionof these cardiac receptors. Moreover, mor-phological and cellular adaptations related totraining seem, to some extent, to be similar asnoted in hearts affected by diabetes or in heart

failure. However, the modifications inducedby physical training, are involved in beneficialcardiovascular modulations.

C-Protein phosphorylation by PKA modu-lates cardiac contractile activity. O. Cazorla,S. Szilagyi, N. Vignier, G. Vassort, L. Carrier,A. Lacampagne (Inserm U-637, CHU Arnaudde Villeneuve, 34295 Montpellier, France).

β-adrenergic stimulation modulates cardiaccontractility through protein kinase A (PKA),which phosphorylates several cellular proteins,such as cardiac troponin I (cTnI) and cardiac C-protein (cMyBP-C). The relative contributionsof cTnI and cMyBP-C to the regulation of my-ofilament Ca2+ sensitivity are still controversialbecause of difficulty in targeting phosphoryla-tion to specific proteins. In the present work,we studied the PKA effect on myofilament Ca2+

sensitivity of the left ventricular skinned my-ocytes isolated from wild type mice (WT) andcMyBP-C deficient mice (KO) at two sarcom-ere lengths (SL: 1.9 and 2.3 µm). Without PKAstimulation and at the shorter SL, Ca2+ sensi-tivity was higher in KO than in WT. No differ-ence in passive tension or maximal active ten-sion was observed. PKA stimulation induced adesensitisation to Ca2+ of WT myofilaments atboth SL. It had almost no effect on KO myofil-aments even though cTnI was phosphorylatedto a similar level in both WT and KO hearts.These observations were similar whether ob-tained on 5-week old mice that showed a lightcardiac hypertrophy or on 55-week old micewith clear signs of cardiac insufficiency, indicat-ing that these observations do not depend uponthe cardiac physiopathological state. The resultssuggest that cMyBP-C contributes to the regula-tion of cardiac contraction during β-adrenergicstimulation and its phosphorylation, as well asthat of TnI, is required for the decrease in Ca2+

sensitivity reported under these conditions.

Effect of different frequencies of exercise onendothelium-dependent vasodilation in ratthoracic aorta. E. Heylen, F. Guerrero, J.

Article published by EDP Sciences and available at http://www.edpsciences.org/rnd or http://dx.doi.org/10.1051/rnd:2006012

284 Abstracts

Mansourati, B. Saïag (UPCI EA3879, 20 Av.Le Gorgeu C.S. 93837, 29238 Brest Cedex 3,France).

The effects of exercise training frequency on en-dothelial function were investigated by measur-ing isometric tension in rings of the thoracicaorta isolated from male Wistar rats submittedto different treadmill training protocols. Vascu-lar responses to ACh (10−9–10−4 M) and SNP(2.10−8 M) were examined in rings precon-tracted with PE (10−7 M). Dose-response curvesto ACh (10−8 to 10−5 M) were also performedin the presence of 5.10−5 M of L-NAME,10−5 M of indomethacine or 10−6 M TEA. In 3groups, rats were submitted to an 8-week tread-mill training protocol (15 m.min−1, 15% in-cline, 60 min.day−1). The animals in these ex-ercise groups ran either 1 day.week−1 (Ex1),3 day.week−1 (Ex3), or 5 day.week−1 (Ex5).A fourth group was composed of age matchedsedentary animals, [restricted to cage activityduring 8 weeks (Sed)]. The aimals in the controlgroup (Control) were of the same age as thosein the Ex and Sed groups before the 8 weekprotocol. SNP-induced vasodilation was neithermodified by aging (Sed group) nor by chronicexercise. The maximal response to ACh wasnot different between groups, while EC50 valueswere inversely correlated with the frequencyof training. In Young as well as Ex3 and Ex5rats, responses to 10−6 and 10−5 M ACh con-centrations were significantly inhibited by L-NAME, indomethacine and TEA. In Sed ani-mals, 10−5 M of ACh-induced vasodilation onlywas inhibited by L-NAME. These results indi-cate that (i): the decrease in endothelium sen-sibility to ACh with ageing is due to impairedeNOS, COX and EDHF pathways and (ii): thiseffect is totally reversed by a training frequencyof 3 or more bouts weekly.

Inducible production of erythropoietin us-ing intramuscular injection of block copoly-mer/DNA formulation. B. Pitard, P. Richard,L. Desigaux, C. Gourden (Institut du Tho-rax, Inserm U533, Faculté de Médecine, 44000Nantes, France).

We have previously shown that intramuscularinjection of plasmid DNA formulated with

a non ionic amphiphile synthetic vector[poly(ethyleneoxide)13-poly(propyleneoxide)30 -poly(ethyleneoxide)13 block copolymer; PE6400]increases reporter gene expression comparedto naked DNA. We investigated this simplenon-viral formulation for production of se-creted proteins from the mouse skeletal muscle.Plasmids encoding either constitutive humansecreted alkaline phosphatase or murine ery-thropoietin inducible via a Tet-on system, wereformulated with PE6400 and intramuscularlyinjected into the mouse tibial anterior muscle.PE6400/DNA formulation led to an increasedamount of recombinant alkaline phosphatasesecreted from skeletal muscle as compared tonaked DNA. In the presence of doxycycline,a single injection of 10 µg plasmid encodinginducible murine erythropoietin formulatedwith PE6400 significantly increased the hemat-ocrit, whereas the same amount of DNA in theabsence of PE6400 had no effect. The increasein the hematocrit was stable for 42 days.The tetracycline-inducible promoter permittedpharmacological control of the hematocrit levelafter DNA intramuscular injection. However,4 months post-injection, the hematocrit re-turned to its pre-injection value, even in thepresence of doxycycline. This phenomenonwas likely caused by an immune responseagainst the tetracycline-activated transcriptionfactor. Intramuscular injection of plasmid DNAformulated with PE6400 provides an efficientand simple method for secretion and productionof non-muscle proteins.

Opposite alterations of vascular globalβ-adrenergic and β3-adrenergic responseearly and late stages of congestive heartfailure in rats. C. Sèze, A. Bammert, G.Toumaniantz, L. Audigane, S. Serpillon, C.Gauthier (Institut du Thorax, Inserm U533, Fa-culté de Médecine 44035 Nantes, France).

Congestive Heart Failure (CHF) is charac-terised by cardiac function and structure alter-ations, but also by an increase in peripheral vas-cular resistance. This study investigated the vas-cular β-AR remodelling in a rat CHF modelproduced by ligating the left coronary artery.Two or 12 weeks after infarction (2W or 12W),

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the thoracic aortae rings of rats were placedin organ baths to measure isotonic contraction.Three groups of rats were designed: SHAM(thoracotomy without ligature), compensatedCHF (PED >15 mmHG: ICC) and overt CHF(CHF and pleural effusion: ICD). The ringswere contracted with phenylephrine (α1-AR ag-onist) and concentration-relaxation curves toisoproterenol (ISO, specific β-AR agonist) andSR 58611A (SR, β3-AR agonist) were per-formed. At an early stage of CHF (2W), a max-imal ISO response was potentialised (ICC 85 ±3% (n = 6), SHAM 78 ± 2% (n = 8), P < 0.05)whereas at 12W it was blunted (ICD 42 ± 3%(n = 6), ICC 48 ± 2% (n = 6), P < 0.05) ver-sus SHAM (57 ± 4% (n = 8)). Surprisingly,maximal SR response was decreased at 2W inICC (67 ± 8% (n = 6), P < 0.01) compared toSHAM (81 ± 2% (n = 7)), but was restoredat 12W (ICD 87 ± 3% (n = 7), ICC 89 ±3% (n = 6), SHAM 87 ± 1% (n = 7)). At2W, the SR-induced relaxation was only signif-icantly blunted in SHAM by pretreatment with100 µM of L-NMMA (NO synthase inhibitor)suggesting the recruitment of another signallingpathway in the β3-AR response in ICC (Emax:SHAM 55 ± 6% (n = 4), ICC 61 ± 6% (n =6)). In conclusion, we demonstrated that vascu-lar global β-AR and β3-AR -induced relaxationwere modified at early and late stages of CHFin an opposite manner. Additional experimentswere clearly needed to determine the cellularmechanisms involved in these alterations.

Heart rate variability in mice: limits and dif-ficulties. J. Thireau, B.L. Zhang, D. Poisson,D. Mohty, P. Cosnay, D. Babuty (UMR-CNRS 6542, Physiologie des cellules car-diaques et vasculaires, Université François-Rabelais, 37200 Tours, France).

The study of heart rate variability (HRV)is useful for the evaluation of the rhythmicprognosis of cardiac diseases and the drugeffects on cardiac rhythm and neurovegeta-tive system. For several years, this methodused in Humans has been applied in labo-ratory animals. However, it is unsuitable be-cause of the high cardiac frequency in mice(600 bpm) and justifies to be modified. The

aim of this work was to estimate the relia-bility of HRV analysis in mice by using theECG-auto 1.5 software (EMKA-Technologies).Electrocardiograms were recorded by telemet-ric techniques (DSI). HRV analysis assumes si-nus rhythm. Thus, the artifacts and arrhythmiahad to be eliminated. In the time domain, weretained the RR intervals between the mean RRinterval ± 2 SD, over long periods (2 × 12 h)and the parasympathetic marker was adapted tothe cardiac frequency of mice (pNN 6 ms). Inthe frequency domain, the analysis with a FastFourier transform and over long periods (ad-vised for man) was inadequate because only oneULF band was individualised which is due tothe non stationarity of the signal. So we selectedseveral short stable periods of three minutes dis-tributed over 24 h. The reproducibility of the re-sults of HRV were dependent on the method ofanalysis: in the time domain, the short period(from 30 to 60 min) of analysis was not repro-ducible but, in the frequency domain the resultsobtained from repeated short period recordingswere reproducible. In conclusion, HRV analysisin mice is possible in the time and frequency do-mains. This analysis was expensive at the timeand requires cautiousness for the result interpre-tation.

Session II. Digestion, nutrition,metabolism and thermoregulation

Docosahexaenoic acid modulates intracellu-lar calcium concentrations via activation ofPKCγ and PKCδ in U937 cells. V. Aires,A. Hichami, R. Filomenko, A. Bettaieb, N.A.Khan (Département de physiologie, UPRESLipides et Nutrition, Université de Bourgogne,6 Bd Gabriel, Dijon, France).

Stimulation of plasma membrane receptorslinked to phospholipase C and the subse-quent production of the second messengerslike diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3) is a signalling pathway offundamental importance in eukaryotic cells.Downstream signalling involves mobilisationof Ca2+ from intracellular stores (mainly en-doplasmic reticulum pool) and Ca2+ influx

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through the opening of store-operated Ca2+

(SOC) channels. Several studies have shownthat protein kinase C (PKC) modulates var-ious ion channel activities including SOC.The present study was conducted in mono-cytic leukemia U937 cells to investigate theeffects of docosahexaenoic acid (DHA), ann-3 polyunsaturated fatty acid, on calcium sig-nalling and to determine the implication of PKCin this pathway. Fura 2 fluorescence ratiometryshowed that DHA stimulated SOC influx via theopening of calcium release-activated calcium(CRAC) channels. Pretreatment of cells withthe PKC inhibitors (GF109203X, CalphostinC and Chelerythrin) significantly inhibited theDHA-induced calcium peak. To gain insightinto the specific isoform(s) of PKC involved inDHA-induced response, we examined the ef-fects of isoform-specific inhibitors. Incubationof cells with HBDDE (PKCα and γ inhibitor)and Rottlerin (PKCδ inhibitor) significantly di-minished DHA-induced rise in [Ca2+]i. How-ever, Hispidin (PKCβI/II inhibitor) and Gö-6976 (PKCα and βI inhibitor) failed to affecta DHA-evoked calcium peak. In vitro PKC ac-tivity assays also revealved a 2-fold increase inPKCγ and δ activities following stimulation byDHA. Together these results suggest that DHA-induced calcium influx occurs via the openingof CRAC channels and activation of PKCγ andδ in U937 cells.

Modulation of gestational diabetes andmacrosomia by n-3 fatty acids. A. Hichami,N.A. Khan (Département de Physiologie, UP-RES Lipides et Nutrition, Université de Bour-gogne, Dijon, France).

Maternal diabetes during pregnancy is an im-portant risk factor for foetal over nutritionleading to fœtal obesity and hyperinsulinemea.Foetal hyperinsulinemia is associated with thedevelopment of glucose intolerance, obesityand diabetes during childhood and adulthood.We used an animal model in which mild hyper-glycemia in pregnant rats resulted in obese hy-perglycaemic and hyperinsulinemic offspring.Diabetic mothers and their obese offspring havean impairment of lipid metabolism and an ab-normal T-cell functioning. Since n-3 polyinsat-

urated fatty acids (n-3 PUFA) are known fortheir immunosuppressive effects and may ex-ert beneficial effects on serum lipids, we in-vestigated the effects of diet containing thesen-3 PUFA on the time course of changes inlipoprotein metabolism and T-cell activation indiabetic mothers during pregnancy and theirmacrosomic offspring during childhood andadulthood. We observed that the n-3 PUFAdiet diminished glycaemia of diabetic rats butdid not affect body weight and glycaemia ofmacrosomic pups. Furthermore, compared withcontrol rats, diabetic rats and their obese off-spring showed a significant elevation in liver,and serum triglyceride and cholesterol concen-trations mostly reflected in VLDL and LDL-HDL1 fractions. We also observed that the n-3PUFA diet restored T cell proliferation whichwas decreased in both pregnant rats and theirobese offspring. Diabetes also decreased the ra-tio of IL4/IL2 mRNA in spleen T cells, whereasthe n-3 PUFA diet increased this ratio in thefavour of T-cell differentiation toward the Th2phenotype. Hence, we can consider the use ofthe n-3 PUFA diet in medical counselling

Control of food intake by fatty acid oxida-tion in a rat model resistant to diet-inducedobesity (Lou/C). G. Lacraz, K. Couturier, R.Favier, X. Leverve (Inserm E-0221, Bioénergé-tique Fondamentale et Appliquée, UniversitéJoseph Fourier, Grenoble, France).

Mitochondrial fatty acid oxidation in the liveris thought to play a significant role in thecontrol of food intake and a low postpran-dial oxidation of ingested fat may contributeto the overeating on a high-fat diet (Scharrerand Langhans, 1987). The purpose of thepresent experiment was to evaluate this hy-pothesis in a strain of rats (Lou/C), charac-terised by a self-caloric restriction (Couturieret al., 2002). Adult rats (Lou/C and Wistar)were fed either a high-carbohydrate, low-fatdiet (HC), or allowed to choose between theHC-diet and a high-fat diet (HF). Fatty oxida-tion was assessed in vitro in rat liver mitochon-dria by studying the respiration rates with lipidsubstrates (octanoyl- and palmitoyl-carnitine)in the presence of increasing concentrations

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of acyl-CoA-dehydrogenases inhibitor mercap-toacetate (MA). The orexigenic effects of MAwere evaluated in vivo by measuring cumula-tive food intake during 6 h after MA injection(200, 400 or 600 µmol.kg−1, i.p.). With bothoctanoyl- and palmitoyl-carnitine, the ADP-stimulated respiration (State 3) was inhibited byMA on the LF diet but (i) the requisite MA dosefor inhibition is higher in Lou/C than Wistar ratsand (ii) hepatic fatty oxidation in the Lou/c ratremains significantly higher than the Wistar ratirrespective of the MA dose. In vivo, the MA(400 and 600 µmol.kg−1) dose-dependently in-creased food intake in Wistar rats whereas MAdid not trigger any orexigenic effect in Lou/Crats. The HF diet increased β-oxidation in theliver in both rat strains. However, O2 consump-tion remains higher in Lou/C rats in the pres-ence of MA. The sensitivity to the orexigeniceffects of MA was increased by high fat feed-ing but the response remained lower in Lou/Cat middle and high MA dose. It is likely that thehigher capacity of β-oxidation displayed by theLou/C rat is responsible for the low caloric in-take displayed by these rats. The mechanismsby which β-oxidation is perceived by liver cellsis currently unknown but could be linked eitherto energy status (ATP-to-ADP ratio) and/or tothe alteration of membrane potential of hepato-cytes. In contrary, the lower sensitivity of Lou/Crats to the orexigenic effects of MA could bedue to higher acyl-CoA dehydrogenase activity.These hypotheses are currently under investiga-tion.

Effect of a weight-reducing program inobese sedentary pre- and postmenopausalwomen. S. Lemoine, N. Rossell, V. Drapeau,M. Poulain, F. Sanguignol, P. Mauriège (UFRStaps, Université Paul Sabatier, Toulouse,France).

The aim of this study was to examine the im-pact of a multidisciplinary weight-reducing pro-gram on body composition, physical capacities,health-related quality of life (HRQL), and eat-ing behaviors of obese pre- (38.5 ± 4.5 years,n = 13) and postmenopausal (55.5 ± 4.3 years,n = 27) sedentary women. All subjects receivedan energy supply close to 1400 ± 200 kcal/day,

6 days per week, during 3 weeks. This pro-gram also included 45 min cycle-ergometer en-durance and 25 min walking sessions at 50% ofheart rate determined at the end of the six-minwalking test (6MWT). Body mass index (BMI),fat mass and lean mass assessed by biolectricalimpedance, distance walked to 6MWT, HRQLevaluated by the SF-36 questionnaire (physicaland mental component scores, PCS and MCS),and eating behaviors (dietary restraint, disin-hibition and susceptibility to hunger measuredby the Three-Factor Eating Questionnaire) weredetermined before and after weight loss. BMIand fat mass decreased (P < 0.0001) while thedistance walked to 6MWT increased in bothgroups (P < 0.001). Although the MCS washigher in both groups (P < 0.0001), the PCSonly increased in postmenopausal women af-ter weight reduction (P < 0.001). The restric-tion score was increased (P < 0.0001), whereasdisinhibition and susceptibility to hunger scoreswere decreased in pre- and postmenopausalwomen after weight loss (P < 0.001 and P <0.01, respectively). Our study shows the effi-ciency of a multidisciplinary weight-reducingprogram on anthropometric and physical mark-ers, as well as on HRQL and eating behavior,irrespective of the women’s age.

In vivo nutritional control of ChREBP ex-pression: implication in the control of lipoge-nesis. D. Letexier, O. Peroni, C. Pinteur, B.B.Kahn, M. Beylot (Inserm U499, Faculté RTHLaennec, Rue G. Paradin, 69372 Lyon Cedex08, France).

The stimulatory effect of glucose on the ex-pression of the lipogenic gene is mediated byChREBP (carbohydrate response element bind-ing protein) at least in the liver. Glucose is aknown stimulator of ChREBP activity but lessis known on its expression control; in vitro ex-periments suggest that its expression is stimu-lated by insulin and glucose and inhibited byfatty acids. We examined the in vivo nutritionalcontrol of ChREBP expression in (i) liver andadipose tissue of Wistar rats (fed and fasted for48 h) and obese Zucker rats, (ii) adipose tissueof fed mice with specific overexpression (Glut-4 ++) or invalidation (Glut-4 -/-) of Glut-4 in

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adipose tissue. Adipose tissue ChREBP mRNAconcentrations were increased in Glut-4++anddecreased in Glut-4-/- mice suggesting that theuptake and metabolism of glucose adipocyteparticipate to the control of ChREBP expres-sion. FAS and ACC1 mRNA levels were modi-fied as ChREBP expression whereas SREBP-1cwas unchanged suggesting that ChREBP con-trols FAS and ACC1 expression in adipose tis-sue. In contrast to these results in geneticallymodified mice, ChREBP expression was notmodified by fasting or high fat diet in both liverand adipose tissue of Wistar rats; the variationsof FAS and ACC1 mRNA were positively re-lated to SREBP-1c but not ChREBP expres-sion. Lastly, ChREBP expression was increasedin the liver but not in the adipose tissue ofobese Zucker rats compared to lean rats. Evenif glucose could participate in its regulation,ChREBP expression appears poorly responsiveto physiological variations of nutritional condi-tions. These results support a role of ChREBPin the development of hepatic steatosis andhypertriglyceridemia but not of obesity in theobese Zucker rat model.

Microsomal prostaglandin E2 synthase-1(mPGES-1) expression is essential forimmune-induced anorexia. E. Pecchi, M.Dallaporta, S. Thirion, C. Salvat, F. Berenbaum,A. Jean, J.D. Troadec (UMR 6153 CNRS-1147Inra, Aix-Marseille III; UMR 7079 CNRS,Paris VI, France).

Infection and inflammation induce a set ofnon-specific symptoms. Among the behaviouralchanges observed, anorexia appears advanta-geous for the host by limiting energy consump-tion devolved to the research of food and byreducing the nutriments available for microor-ganisms. However, chronic anorexia compro-mises immune defences, reduces muscle massand therefore may represent a significant healthrisk. Thus, it appears critical to characterisethe molecular mechanisms underlying anorexiaduring infection. Prostaglandins constitute animportant inflammatory mediator family whoselevels increase in the brain during inflammatorystates. The prostaglandin E synthases (PGES)are involved in the production of PGE2 from

PGH2. Microsomal PGES-1 (mPGES-1) hasbeen described as an inducible enzyme whoseexpression is stimulated by pro-inflammatoryagents in several tissues. The present study at-tempted to determine whether an up regula-tion of mPGES-1 gene expression may accountfor immune induced anorexic behaviour. In re-sponse to anorexic doses of pro-inflammatorycytokines (IL-1β), mPGES-1 gene expressionis up-regulated in the two main central struc-tures involved in the control of food intake i.e.the DVC, a brainstem structure lining the 4thventricle, and the hypothalamus. Interestingly,injection of IL-1β into the 4th ventricle re-sulted in an mPGES-1 expression increase anda concomitant reduction in food intake suggest-ing that the DVC plays a preponderant role inthe onset of anorexic behaviour. Noteworthy,Il-1β failed to decrease food intake in mPGES-1KO mice (Pfizer, Groton, USA). Altogether,our results demonstrate that mPGES-1 which isstrongly up-regulated in the hypothalamus andthe DVC is essential for immune anorexic be-haviour and thus constitutes a potential thera-peutic target.

Whole-body and lower-limb body composi-tion assessment in senior women. M. Rance,B. Morio, D. Courteix, M. Bedu, E. Van Praagh,P. Duché (Laboratoire Interuniversitaire de Bi-ologie des Activités Physiques et Sportives,UFR Staps Clermont-Ferrand, BP 104, 63172Aubière Cedex, France).

To evaluate in female seniors, the accuracyand bias of anthropometry and bioelectricalimpedance analysis (BIA) for whole-body andlower-limb body composition measures usingdual-energy X-ray absorptiometry (DXA) asthe criterion method. Nineteen women (66.1 ±4.2 y) participated in the study. Whole-body fatmass (FM) and fat-free mass (FFM) were mea-sured by anthropometry (A), BIA and DXA.Lower-limb volume (LLV) and FFM (LLFFM)were assessed by anthropometry and DXA.No significant difference was observed betweenFMA vs. FMDEXA and FFMA vs. FFMDEXA (r2 =

0.93, P < 0.001, CV = 7.3% and r2 = 0.85, P <0.001, CV = 4.4%, respectively). No significantdifference was observed between FMBIA and

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FMDEXA (r2 = 0.80, P < 0.001, CV = 11.6%).FFM was significantly underestimated by BIAvs. DXA (P < 0.01). LLV and LLFFM weresignificantly overestimated by anthropometryvs. DXA (P < 0.05 and P < 0.001, respec-tively) but significant relationships (r2 > 0.25,P < 0.001) were observed. The difference be-tween the right and left lower-limb measureswas not affected whatever the method used. Inconclusion, in female seniors, (i) anthropometryrepresents an accurate method to assess whole-body composition which has to be improvedby corrective equations before being used toaccurately estimate lower-limb body composi-tion; (ii) despite non significant bias for fat massmeasurement, bioelectrical impedance analysistends to overestimate fat mass and underesti-mate fat-free mass.

Session III. Endocrinology

Evolution kinetics of women waist measure-ment according to body mass index duringendurance training. E. Abid, K Masmoudi,N. Zouari (Functional Exploration Department,CHU H. Bourguiba, 3029 Sfax, Tunisia).

Woman waist measurement (WM) higher than88cm belongs to elements of metabolic syn-drome definition. The aim of our study is tocompare the evolution kinetics of WM of obesewomen, those with weight excess and thosewith normal weight during 6 months trainingin endurance: Twenty-nine women (age: 36.8 ±2.55 y), distributed into 3 groups of respectively9, 10 and 10 subjects recording to BMI (G1:22.83 ± 0.42; G2: 26.7 ± 0.42; G3: 33.84 ±0.83 kg·m−2) were recruited. An enduring ex-ercise was carried out during 5 meetings perweek of 1 h each during 6 m. Measurements ofweight, BMI, WM, hip measurement and fattymass percentage were taken before and thenmonthly during training. We found a significantdecrease of all parameters in Gl and G2. How-ever, in G3, the loss of weight and BMI was notsignificant in spite of the significant reductionof other measurements. Concerning the WM,its decrease every month was always significantfor the 3 groups with a value of P < 0.001during the first months and P < 0.05 during

the last months. At the end of 6 months, thefall of the absolute value of WM was moremarked for G3 but it was comparable betweenthe 3 groups if expressed as a percentage. Inconclusion, a maintained physical activity inendurance always has a beneficial effect on theWM. Thus, the perceptible absence of fall ofweight among obese women should not dis-courage them especially since it has a signifi-cant reduction of WM which would testify toan improvement of the metabolic syndrome.

Effect of pioglitazone treatment on adiposetissue glucocorticoid (GC) metabolism inadult rats with postnatal diet-induced over-weight and metabolic syndrome. S. Boullu-Ciocca, V. Achard, A. Dutour, M. Grino (Lab-oratory of Hematology, Inserm UMR 626,Faculty of Medicine, University de la Méditer-ranée, 13916 Marseille, France).

Local reactivation of inert into active GC invisceral adipose tissue (VAT), driven by 11beta –hydroxysteroid dehydrogenase type 1(11 beta-HSD-1), plays a pivotal role in thepathophysiology of obesity and the metabolicsyndrome. The metabolic actions of pioglita-zone are well documented; however, their un-derlying mechanisms are only partially known.Some experimental studies (in vivo using agenetic model of obesity or in vitro) suggestthat 11 beta-HSD-1 can be implicated. Westudied the effects of pioglitazone in a modelof environmentally (postnatal overfeeding)- in-duced overweight and metabolic syndrome.Early postnatal (P3-P21) normofed (NF) oroverfed (OF) adult rats were treated with pi-oglitazone for 5 weeks (3 mg.kg−1.day−1 peros; Takeda Chemical Industries, Japan). In NFrats, pioglitazone treatment induced a bodyweight increase but did not affect metabolicand hormonal parameters. OF rats were over-weighted, showed glucose intolerance togetherwith increased VAT mass and 11 beta-HSD-1mRNA expression (44.48 ± 3.08 vs. 35.20 ±0.64 nCi.g−1 in untreated NF; P < 0.001). Pi-oglitazone treatment induced a body weight in-crease, normalised glucose tolerance, enlargedsubcutaneous AT mass, and decreased VATmass and 11 beta-HSD-1 mRNA expression(37.58 ± 0.64 nCi.g−1; P < 0.05 vs. untreated

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OF rats). These results show that pioglita-zone treatment down-regulates adipose tissue11 beta-HSD-1 expression in a postnatal diet-induced model of overweight and metabolicsyndrome. They suggest that drug-induced al-terations in local GC metabolism, specifically inVAT, induces, at least in part, fat mass changesand insulin sensitivity improvement.

Altitude-induced anorexia in obese Zuckerrats. N. Simler, A. Grosfeld, M. Guerre-Millo,A.X. Bigard (Centre de Recherches du Ser-vice de Santé des Armées, 38702 La Tronche,France).

Altitude-induced anorexia is well described inhumans and in rodents but the initiating pro-cesses remain unknown. A growing number ofrecent works reported a stimulation of the pro-duction of the leptin protein, an adipokine in-ducing satiety, under low oxygen availability invitro. We assessed the effects of hypobaric hy-poxia (from 1 to 4 days) in lean FA/FA and inobese fa/fa Zucker rats lacking on leptin signal-ing. Obese and lean rats exhibited a same im-mediate and marked anorexia. In lean rats, novariation in leptin expression and/or in circu-lating levels could be seen. Obese rats showedsignificant increases in both leptin productionand release, and in the hypoxia-inducible geneVEGF expression in white adipose tissue. Inthe hypothalamus, the expression of the orexi-genic NPY did not drop at the onset of hypoxiawhatever the genotype, and POMC, AGRP,CART and CRF mRNA did not vary. We con-cluded that altitude-induced anorexia was nei-ther driven by leptin nor by hypothalamic neu-ropeptides regulating food intake. Nevertheless,the marked stimulation of the leptin gene ex-pression and synthesis in obese rats is in favorof an acute action of ambient hypoxia on leptingene expression. This specific action of hypoxiain obese rats could be related to the weaknessof some counter-regulatory hormonal pathwaysin the obese phenotype such as the β-adrenergicpathway or to a hypersensitivity of the hypertro-phied white adipose tissue toward hypoxia dueto reduced local blood flow.

Cell swelling induced peptide hormone se-cretion. V. Strbak, J. Benický, S.E. Greer, Z.

Bacova, M.A. Greer (Institute of ExperimentalEndocrinology, Slovak Academy of Sciences,Bratislava, Slovakia).

Alterations of cell volume represent an inde-pendent signal contributing to the regulation ofcell function. Cell swelling (induced by hypo-tonic medium or ethanol in isosmotic medium)evokes the secretion of hormones and pep-tides stored in secretory vesicles from vari-ous types of cells (endocrine, neurons, leuko-cytes, exocrine pancreas). The dynamics ofthis secretion is indistinguishable from thoseinduced by specific secretagogues. This typeof regulated secretion possesses several spe-cific features. It does not require a rise in in-tracellular Ca2+ through the opening of Ca2+

channels. Using various tissues (pituitary, pan-creatic islets, heart and brain structures), hor-mones (prolactin, insulin, thyrotropin releas-ing hormone – TRH, oxytocin) and inhibitors,we found that hormone secretion inducedby cell swelling is not depressed by inhibi-tion of stretch activated channels, mercury-sensitive aquaporins, protein kinase C, mi-crotubules and microfilaments and does notinvolve prostaglandins and leukotriens. Block-ing Na+-K+-dependent ATPase, Na+ channels,K+ channels or K+/Na+/2Cl− co transport hadno inhibiting effect on hyposmolarity-inducedhormone secretion in pituitary or pancreaticcells. Careful comparison of glucose and hypo-tonicity induced secretion revealed a novel sig-naling pathway for the stimulation of insulin se-cretion exploited by cell swelling. Hyposmoticstimulation is independent of both extracellu-lar and intracellular Ca2+, does not involve PKCactivation, and could not be inhibited by nora-drenaline. Participation of such a general phe-nomenon raises the question of specificity. Cellswelling induced by hypotonicity or isosmoticethanol containing medium evoked the releaseof TRH but not oxytocin from the hypothala-mic paraventricular nucleus and posterior pitu-itary. Swelling induced oxytocin release couldbe uncovered by inhibiting stretch receptors ac-tivated channels by GdCl3. In conclusion, cellswelling consistently triggers peptide secretionfrom various types of cells exploiting a differenttransduction pathway than that delineated forother natural or pharmacological secretagogues.

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Signaling is likely to act at a distal end of thesecretory pathway. This stimulation possesseslimited selectivity. By overriding physiologi-cal inhibition, cell swelling induced secretionmight represent important pathophysiologicalmechanisms.

Session IV. Muscular exercise

Effect of sprint training and detraining oncatecholamine responses to sprint exercise inadolescent boys. M. Botcazou, H. Zouhal, C.Jacob, A. Gratas-Delamarche, S. Vincent, D.Bentué-Ferrer, P. Delamarche (Laboratoire dePhysiologie, Université Rennes 2, Av. C. Tillon,35043 Rennes Cedex, France).

Catecholamines (adrenaline (A) + nora-drenaline (NA)) are known to play a majorrole during exercise by controlling hepaticand muscular glycogenolysis (Sonne et al.1985). Physical training is a potential factorable to alter the sympathoadrenergic activityin response to exercise. Indeed, Strobel et al.(1999) and Zouhal et al. (2001) demonstratedthat essentially the intensity of training, suchas sprint training, may alter catecholamineresponses to exercise. In children, pubertalmaturation induces hormonal and metabolicmodifications and may influence catecholamineresponses to exercise. Thus, we studied thecombined effect of sprint training (6 months)and maturation in adolescent boys on plasmaA, NA and blood lactate (La) in response toa 6 s-sprint on a cycle ergometer. Thirteenhealthy boys (Tanner Stage 4, training group(TG), n = 6, control group (CG), n = 7) tookpart in our study and performed a 6s-sprint testbefore training (P1), after the training period(P2) and after 5 months of detraining (P3) forTG only. Maximal power (Wmax) determinedduring the 6s-sprint test increased significantlyin TG after P2. The performances did notchange in CG; Wmax was significantly higherin TG after P2 compared to CG. In responseto the 6s-sprint test, La and NA concentrationsincreased significantly in TG and CG after P1and P2 and were similar between the groups.However, the 6s-sprint induced significantplasma A increase in TG and CG, only after P2,

and in TG after P3. Our data strongly indicatethat in adolescent boys, sprint training mayenhance performances but not catecholamineresponse to short cycle ergometer sprintingsuggesting an eventual pubertal maturationeffect on sympathoadrenergic activity.

VO2 slow component and fibre recruitment.G. Deley, G.Y. Millet, F. Borrani, G. Lattier,L. Brondel (Inserm/ERITm 0207, UFR Staps,21000 Dijon, France).

During high-intensity exercises, the oxygen up-take kinetics is characterised by a slow compo-nent, which delays or prevents the attainmentof the steady state. The aim of this study was touse prior fatiguing exercises to test the hypothe-sis that recruitment of type II fibers participatesin the VO2 slow component phenomenon. Ninesubjects performed three randomised cyclingexercises at a work rate corresponding to 80%of their maximal aerobic power: (i) precededby a fatiguing protocol using electromyostim-ulation (EMS), (ii) preceded by a fatiguing pro-tocol using voluntary contractions (VOL) and(iii) without the fatiguing protocol (CONTR).The fatiguing protocols consisted in an alterna-tion of 10 s of isometric contractions and 10 sof recovery during 20 min, at 10% of a max-imal voluntary contraction (MVC), on the twoknee extensors. Respiratory gas exchanges weremonitored breath-by-breath during the cyclingtests and then analysed with a bi-exponentialmodel. The main result is that a 20-min priorexercise with electrically-induced or voluntarycontractions at a same % of MVC induced sim-ilar force reduction but affected the VO2 ki-netics differently. The amplitude registered af-ter EMS was significantly reduced and delayedcompared with those obtained in CONTR andVOL conditions (P < 0.05). Moreover, the cy-cling test was significantly shorter for EMS thanfor CONTR and VOL (P < 0.01). According toseveral studies on the recruitment order, it canbe considered that a fatiguing protocol usingvoluntary or electrically evoked contractions af-fects a different pool of motor units. These re-sults suggest that type II fiber recruitment maybe at least in part implicated in the VO2 slowcomponent phenomenon.

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Effect of endurance training on oxydativephosphorylation and H2O2 production in iso-lated rat liver mitochondria. H. Dubouchaud,T. Coisne, R. Favier, X. Leverve (LBFA-InsermEMI 0221, Université Joseph Fourier, BP 53,38041 Grenoble Cedex 9, France).

Reactive oxygen species (ROS) are known to beinvolved in muscle tissue damage induced byexercise. They are also considered as importantfactors for the control of cellular functions. Themitochondria is one of the major sites of ROSproduction in cells. Despite the central role ofthe liver in the whole body metabolism, littleis known about the effects of chronic exerciseon mitochondrial ROS production in this tissue.The aim of this study was therefore to measureoxygen consumption (JO2) and H2O2 produc-tion in isolated liver mitochondria from trained(treadmill running at 25 m.min−1, 1 h.day−1,5 days.week−1 for 6 weeks) and control rats.Specific substrates and inhibitors of the differ-ent complexes of the electron transport chain(ETC) were used to characterise the sites of al-terations. The results show that endurance train-ing increased citrate synthase activity in theliver (+17%, P < 0.05) as well as cytochromeC oxydase (+50%, P < 0.05) and superoxydedismutase (MnSOD) (+40%, P < 0.05) activ-ities in the liver mitochondria. With succinate(substrate of complex II), state 3 (phosphory-lating conditions) JO2 was higher in trainedrats (+29%, P < 0.05) while H2O2 productionwas lower (–10%, P < 0.05). With octanoyl-carnitine as a substrate of both complexes I andII, training decreased H2O2 production in thebasal state (–25%, P < 0.05) and in state 3(–28%, P < 0.05). These results suggest thatendurance training induces alterations of theETC in the liver that could contribute to en-hance fatty acid utilisation. These alterationscould also reduce ROS production in the liverwith consequences on cellular functions.

Physical training in adolescent girls withtype 1 diabetes mellitus (IDDM). A. Gratas-Delamarche, E. Heyman, C. Toutain, P.Delamarche (Laboratoire de Physiologie etde Biomécanique de l’Exercice Musculaire,ENS Cachan-UFRAPS, Université Rennes 2,

Campus La Harpe, Av. Charles Tillon, 35044Rennes Cedex, France).

Many studies have indicated that the alterationof physical fitness induced by inactivity fromchildhood to adulthood is exacerbated in pa-tients with IDDM. Especially in girls, puberty isknown to be associated with the appearance ofgrowth hormone and insulin resistance, whichusually leads to excess weight, glycemic con-trol deterioration and dyslipidemia. Moreover,the beneficial effects of a physical training pro-gram have not yet been demonstrated in thisspecific population. Thus, we investigated forthe first time, in IDDM adolescent girls com-pared to a control group, the effects of a 6 monthsupervised training program on physical fitness,body composition, glycemic control, insulin re-sistance factors (leptin, adiponectin, IGF-I) andquality of life. The main results were that thistraining program succeeded to significantly im-prove body composition, physical fitness andquality of life and to stop the pubertal lep-tin increase. Nevertheless, as in other studiesconcerning either adults or male adolescents,no significant effect was shown on glycemiccontrol. Thus, it appears difficult to improveglycemic control in IDDM adolescents usingtraining per se without insulin and diet counsel-ing. Nevertheless, these findings strongly inciteto encourage IDDM adolescent girls to exercise.

Muscle correlates of the increase in VO2max

after combined upper limb resistance andlower limb endurance training in healthyelderly. J. Verney, N. Charifi, J. Castells, F.Kadi, C. Denis (Médecine du Sport et Myolo-gie, Unité de recherche PPEH, Hôpital Belle-vue, 42055 Saint-Etienne Cedex 2, France).

To investigate whether the improvement in legand arm VO2max after upper body strengthand lower body endurance training respectivelyare mediated by similar muscle adaptations?Twelve elderly subjects (73 ± 4 years old)trained 3 times a week during 14 weeks. Train-ing consisted in 3 times 12 min of high in-tensity interval training on bicycle and 3 times12 min of upper body resistance training.Maximal oxygen uptake was measured with

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mechanically braked ergometer for both lowerlimbs and upper limbs (arm cranking). Musclecross sectional area (MCSA) was measured us-ing MRI. Muscle biopsies were taken from thevastus lateralis and deltoideus and immunos-tained with the antibody CD31 for the visual-isation of capillaries and the ratio between thelength of capillaries in contact with fibre andfibre perimeter (LC/PF index) was measured.Muscle samples were also spectrophotometri-cally analysed for citrate synthase (CS) activ-ity. VO2max increased significantly by 9% and16% in legs and arms respectively. MCSA in-creased significantly in deltoideus (+7%) butnot in quadriceps (+2%). The LC/PF index in-creased significantly in legs (+30%) but notin arms (+14%). CS activity increased sig-nificantly in both muscles. In conclusion, thetraining-induced increase in VO2max is accom-panied by capillarisation and metabolic adap-tations in legs and by muscle hypertrophy andmetabolic adaptations in arms.

Nitrate and nitrite response to a 30s-Wingatetest in men and women. S. Vincent, A. Gratas-Delamarche, B. Saiag, J. Callebert, P. Dela-marche (Laboratoire de Physiologie, UniversitéRennes 2, Av. C. Tillon, 35044 Rennes Cedex,France).

NO plays an important role in regulating vas-cular tone during exercise and during recovery.During submaximal aerobic exercises, changesin the plasma concentration of the end prod-uct of NO have been observed in men. Toour knowledge, no study has evaluated thesechanges in response to sprint exercise. How-ever, sprint exercises increase considerably theblood flow, thus sheer stress and catecholaminelevels, activators of NO production. So, the aimof this study was to explore nitrate and nitrite(indicator of Nitric oxide production) responsesto a very stressful exercise in physically activestudents of both sexes. Eight men (22.0 ± 0.6 y;177.7 ± 2.6 cm; 70.1 ± 1.8 kg) and 8 women(19.8 ± 0.7 y; 165.8 ± 1.5 cm; 59.2 ± 1.8 kg)participated in a 30 s Wingate-test on a bicycleergometer. Plasma lactate (by a microenzymaticmethod), nitrates+nitrites (by the Griess col-orimetric micromethod), 17β-estradiol (17βE2)

and progesterone (by RIA) and catecholamine(by HPLC) concentrations were determinedat rest, at the end of the warm-up and ex-ercise periods as well as during the recov-ery (5, 10, 20 and 30 min). The day of theWingate test, all women were in luteal phaseas indicated by their 17β-estradiol and pro-gesterone values (194.4 ± 14.2 pg.mL−1 and13.7 ± 5.0 ng.mL−1 respectively). The resultsshowed that plasma lactate, catecholamines andnitrates+nitrites concentrations increase in re-sponse to a 30 s Wingate-test but did not dif-fer beween gender. In conclusion, the majorfinding of this work was that this type of ex-ercise induced NO production represented byan increase in above 25% of [NO−3 + NO−2 ].This study failed to show any significant NOproduction between both sexes, when exercisegenerates a similar stress level and creates com-parable shear stress.

Session V. Neurophysiology

Animal model of obsessive-compulsive dis-order in the primate. Role of the thalamo-cortical projections. B. Aouizerate, D. Guehl,V. Amestoy, J. Tignol, B. Bioulac, P. Burbaud(Service de Psychiatrie d’Adultes, UniversitéVictor Segalen Bordeaux 2, Centre Hospital-ier Charles Perrens, Centre Carreire, Bordeaux,France).

Obsessive-Compulsive disorder (OCD) is a rel-atively common and severely disabling psychi-atric disease. Although its pathophysiology isstill far from resolved, a dysregulation in thefronto-subcortical circuits originating in the or-bitofrontal cortex (OFC) and the anterior cin-gulate cortex (ACC) is proposed to play a ma-jor role in the pathogenesis of OCD. This workwas aimed at testing the hypothesis that an en-hanced activity in the orbitofrontal and anteriorcingulate loops is a central factor in the me-diation of OC symptoms. For this purpose, apharmacological approach was used in Rhesusmonkeys, mainly based on intra-thalamic infu-sions of the GABAA receptor antagonist bicu-culline in order to induce a disinhibition of thethalamo-cortical projections. The subdivisions

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of the medial dorsal (MD) and ventral anterior(VA) nuclei of the thalamus, which preferen-tially project to the OFC and the ACC, werechosen as targets for infusions. Preliminary re-sults showed an exacerbation of behaviors pre-dominantly oriented towards reward (food) de-livery when bicuculline was infused into themost medial and posterior region of VA (“parsmagnocellularis”), which is the source of vastprojections to the OFC and ACC that are bothimplicated in emotional and motivational com-ponents of behavior. In contrast, infusion ofbicuculline into the anterior but lateral part ofMD (“pars parvocellularis”) led to repetitivebehavioral shifts (exploration – observation –feeding), with an enhanced sensitivity to cer-tain environmental stimuli. This subdivision ofMD is intimately connected to the ACC and thedorso-lateral prefrontal cortex, which is specif-ically involved in a range of functions includ-ing attention, working memory, and planningof action. In conclusion, these findings suggestthe importance of the thalamo-cortical projec-tions from discrete regions of MD and VA inthe emergence of repetitive behaviors that arereflective of either an exacerbation of emotionaland motivational processes, or a putative deteri-oration of executive functions.

Pain associated to limited dorsiflexion of op-erated clubfeet in children. C. Beyaert, T.Haumont, J. Paysant, M.A. Haldric, N. Mar-tinet, J.M. André (Laboratoire de Physiologie,Faculté de Médecine, Av. Forêt de Haye, 54511Vandoeuvre-lès-Nancy, France).

Pain located at the foot instep (P) and limita-tion of foot to tibia dorsiflexion (DF) are of-ten associated in clubfoot. P was hypothesisedto be elicited or increased when maximal DFis forced involving tibio-talar and/or midfootjoints. Seventeen children (12 ± 3 years of age)who reported P on their 21 clubfeet were com-pared to controls. Maximal DF and P were as-sessed when sitting, standing on a slope (bare-foot and with the foot attached on a small boardto allow only tibio-talar joint movement), whenwalking at a self selected pace and running. Pwas elicited for 11 clubfeet among all condi-tions. P was not elicited in sitting (maximal DF

9 ± 9◦) but when standing barefoot (intensity3.1 ± 2.5 (scale 0-10), maximal DF 18 ± 12◦)the intensity of which was reduced with the footattached on a board (1.8 ± 2, P < 0.05; maxi-mal DF 20 ± 11◦). During running, mean P in-tensity (n = 11) was higher (2.6 ± 1.7, 9 painfulclubfeet) than during walking (0.6 ± 1.1, n = 3,P < 0.05) associated with a higher maximal DF(16 ± 7◦ versus 11 ± 5◦, P < 0.01). MaximalDF was higher in controls (P < 0.05) than in thepainful clubfeet group when standing (44 ± 6◦)and running (29 ± 5◦). Pain located at the footinstep was elicited or increased when maximalDF was increased but was still lower than thecontrol values, suggesting painful stress locatedat the tibio-talar and midfoot joints when DFreached its limit. During maximal DF in stand-ing on a slope, reduction in P intensity by im-mobilizing midfoot joints suggests their contri-bution in pain.

Study of the modifications of spontaneousbaroreflex sensitivity and sympathovagalbalance in experienced pilots after an aer-obatic flight. C. Dussault, J.C. Jouanin, D.Tran, C.Y. Guezennec (Imassa, Département dePhysiologie, BP 73, 91223 Brétigny-sur-OrgeCedex, France).

The aim of this study was to document mod-ifications in spontaneous baroreflex sensitivity(BRS) and disturbances of sympathovagal bal-ance in aerobatic pilots after exposure to “push-pull” accelerations. Five aerobatic pilots per-formed during a 30-min flight 5 series of 30 snegative spirals (–4 Gz), followed by 30 s ofpositive spirals (+4 Gz). A stand-test was per-formed before the flight (T0), immediately after(PF), 1 h after (PF1) and 2 h after (PF2). In-flight HR was recorded on a magnetic tape witha TEAC recorder (HR 30G, TEAC Corporation,Japan). A Finapres apparatus recorded heartrate (HR) and blood pressure during the stand-tests. The inflight HR results show that therewas an effect associated with the change from–Gz to +Gz, for all of the spirals (P = 0.003).Moreover, this effect on HR response was ac-centuated during the series (P = 0.031). The re-sults show that resting HR was increased at PF(P < 0.01). The analysis of spontaneous BRS

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did not change at PF compared to T0 but it washigher at PF1 than PF (P < 0.05). Sympatheticmodulation of HR variability (HRV) tended toincrease in the supine position at PF. Parasym-pathetic modulation of HRV increased at PF2(P < 0.001).This study demonstrates that thespontaneous BRS and HRV are modified duringthe recovery phase of aerobatic flight includingthe push-pull manoeuver. The classical increasein sympathetic activity immediately after exer-cise could be attenuated by the high vagal activ-ity during –Gz accelerations. Spontaneous BRSanalysis could be a tool for clinical surveillanceof pilots exposed to push-pull accelerations.

Time-frequency analysis of the central ef-fect of angiotensin I and angiotensin II onheart rate variability in trout. F. Lancien, N.Mimassi, D. Mabin, J.C. Le Mével (Labora-toire de Neurophysiologie, U650, Faculté deMédecine, 22 Av. Camille Desmoulins, 29238Brest, France).

In order to gain new insight into the existenceof a brain renin-angiotensin system (RAS) inteleost fish, we investigated in the unanes-thetised trout the effects of centrally admin-istered angiotensin (ANG) I and ANG II onheart rate (HR) and heart rate variability (HRV)prior to or after pretreatment of the animalswith captopril, an angiotensin-converting en-zyme (ACE) inhibitor. Trout were equippedwith electrocardiographic electrodes and withan intracerebroventricular (ICV) cannula. Theshort-time Fourier transform was used to anal-yse the time course-actions of the angiotensinson HRV. The ICV injection of the vehicle hadno effect on the recorded parameters. The ICVinjections of ANG I and ANG II at a dose of5 and 50 pmol induced a marked action onHR and HRV. At a dose of 50 pmol, ANG Iand ANG II produced a progressive and sig-nificant increase in HR (+36% and +45%, re-spectively) but elicited a profound decrease inHRV (–88% and –92%, respectively). ICV in-jection of captopril (10 µg) had no effect onHR or HRV. However, this ACE inhibitor pre-vented the tachycardia and abolished the de-crease in HRV mediated by 50 pmol of ANG I.By contrast, captopril had no effect upon the

cardiac actions of 50 pmol of ANG II. Theseresults give the first support for a functional im-plication of an ACE-like activity in the brain ofteleost fish and suggest that the brain RAS inthis species of vertebrates may be involved inthe control of cardiac chronotropic activity.

The role of the anterior cingulate cortexin learning from past errors. T. Micheleta,B. Bioulac, D. Guehl, L. Escola, P. Burbaud(a Laboratoire de Physiologie et Physiopatholo-gie de la Signalisation Cellulaire, UMR CNRS5543, Université Victor Segalen Bordeaux 2,146 rue Léo Saignat, 33076 Bordeaux, France).

Learning from our own mistakes is a key fea-ture of human behaviour, although the mecha-nisms underlying short-term adaptation to erro-neous action are still poorly understood. Sincethe descriptions of its involvement in the cod-ing of action outcomes, the anterior cingulatecortex (ACC) is thought to play a central rolein performance evaluation and especially inerror detection. Furthermore, this cortical re-gion occupies a strategic position within a dis-tributed network that integrates environmentalinformation through high-level cognitive andmotivational input. To address this problem,we designed a Stroop-like visuo-motor task inmonkeys which favours incorrect action. Wefound that single neurons recorded in the ACCwere closely tuned to behavioural performance.First, the activity of most neurons was biasedtowards the evaluation of erroneous action. Sec-ond, the effect of a warning stimulus on neu-ronal firing was significantly greater after an er-roneous response than after a successful one,leading to an improvement in subsequent per-formance. Third, a significant proportion ofACC neurons exhibited both these evaluative-and strategic-related activity patterns which arethe minimal requirement for remedial action.Finally, we found that these monitoring relatedactivities were not directly modulated by cog-nitive and motivational information but wererather contingent to the subject’s engagementin the task. This result brings together differ-ent theories of ACC function by demonstrat-ing that effectively, the different components ofaction monitoring are processed by the same

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ACC neurons. Taken together, these data sug-gest that the ACC serves as a powerful compu-tational locus for rapid corrective adaptation tobehavioural error.

An animal model of a spontaneously re-versible obstructive sleep apnea syndrome inthe monkey. P. Philip, C.E. Gross, J. Taillard,B. Bioulac, C. Guilleminault (Clinique du Som-meil, CHU Pellegrin, place Amélie Raba Léon,33076 Bordeaux Cedex, France).

The anatomy of the tongue and uvula in mon-keys share many similarities with humans, sothis species has the closest approximation tothe human upper airway than any other species.In this study, we investigated the feasibility ofusing small monkeys as experimental animalsfor an obstructive sleep apnea model. Monkeysreceived intradermal injections of liquid colla-gen in the uvula, tongue and lateral pharyngealwalls every two weeks. Polysomnography wasperformed bi-monthly in order to control theimpact of injections on breathing events, respi-ratory effort (as measured by esophageal pres-sure) and sleep. Before the injections, the threeanimals showed normal breathing during sleepwith a mean of 4.8 ± 2.0 events.h−1. After theinjections, a mean of 27.9 ± 19.7 hypopneas.h−1

were recorded (P = 0.023). Total sleep timewas significantly reduced, with a decrease ofREM sleep and stage II sleep; however, stage Isleep increased. Collagen injections in the mon-key’s upper airways can create sleep disorderedbreathing and abnormal sleep, as seen in apneicpatients.

Cortico submental conduction in patientswith central neurological swallow dysfunc-tion. E. Verin, J.P. Marie, P. Denis, (Service dePhysiologie Digestive, Urinaire, Respiratoire etSportive, CHU Rouen, 1 rue de Germont, 76031Rouen Cedex, France).

Submental muscles, including constrictor pha-ryngeal muscles, are submitted to an automaticcontrol located in the brainstem and to a bi-lateral cortical control. The aim of our studywas to characterise cortical-submental conduc-tion in stroke patients and to correlate it to swal-

low dysfunction. Fourteen stroke patients withswallow dysfunction (pharyngeal stasis or aspi-ration) were studied (7 f, 67 ± 10 y). Submen-tal surface electrodes permitted to record themylohyoideus motor evoked potential (MEP)after focal transcranial magnetic stimulations.Three stimulations of the right and left hemi-sphere were realised (6 to 8 cm laterally and 2 to4 cm anteriorly from the vertex), permitting torecord left and right MEP and to calculate MEPscore (1 normal response; 2: conduction time >15 ms; 3 no response) for each subject. Swal-lowing function was evaluated using pharyn-geal endoscopy or pharyngeal videomanometry(pharyngeal fluoroscopy coupled with manom-etry), which permitted to classify the subjectsin group 1 (pharyngeal stasis without laryngealaspiration) and group 2 (laryngeal aspirationor bronchial penetration). In 6 patients, MEPwere normal after right and left cortical stimu-lations, and in 8 subjects, an abnormal submen-tal conduction was recorded (rise in latency orno response), right or left, ipsi or contro lateral.MEP score was significantly higher in group2 compared to group 1 (6.6 ± 0.7 vs. 4.6 ±0.3; P < 0.05). In conclusion, mylohyoideusMEP in response to focal cortical stimulationshould help to define the cortico pharyngealpathway lesion. Their conduction time alter-ations were higher in patients with laryngealaspiration or bronchial penetration, underliningthe major role of the oropharynx in the swal-lowing function.

Session VI. Normal and pathologicalweight regulation (neurological and en-docrinological aspects)

Control of food intake by stimuli originat-ing from the splanchnic area. S. Blat, C.H.Malbert (UMR SENAH, Inra, 35590 Saint-Gilles, France).

In addition to the obvious role of the gut in thedigestion and absorption of nutrients, the intes-tine and associated visceral organs, includingthe pancreas, liver and visceral adipose depots,have important sensing and signalling roles inthe control of food intake. To accomplish this

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role, the gut uses neural and endocrine path-ways to communicate with controllers of foodintake in the hypothalamus and hindbrain. Theidea that short-term (e.g., satiety in the imme-diate postprandial period) and long-term (e.g.,satiation maintaining energy homeostasis) foodintake are regulated through distinct mecha-nisms involving the extrinsic nervous systemfor satiety and hormonal mediators for satia-tion is no longer popular and evidence has nowbeen raised that nervous and humoral mech-anisms act interactively to regulate long-termand short-term food intake. Indeed, mediatorsthat produce a direct stimulation of visceral sen-sory nerve endings may do so as part of a dis-crete sensory signalling pathway. In this case,the afferent neuron does not respond directly toa stimulus, but following the release of a me-diator from a primary sense cell. Examples ofthese cells, which effectively act as principalsensory transducers, are enterochromaffin cells,which release 5-hydroxytryptamine and en-teroendocrine cells that release cholecystokinin.However, the stimulation of intrinsic nervescan in turn lead to the secretion of hormonescontrolling satiety and/or satiation. This is thecase for the entero-pancreatic nerves studiedin our laboratory. Entero-pancreatic nerves di-rectly connect the gut to the pancreas, and theiractivation by post prandial stimuli participatesin insulin secretion, a hormone well knownfor controlling satiation. Eventually, synergisticnervous and humoral signals originating fromthe splanchnic area are conveyed to the centralnervous system where they are integrated.

The olfactory system as a sensor of nu-tritional state? A way to regulate food in-take. M. Caillol, C. Baly, J. Aïoun, P. Congar,T. Gorojankina, R. Salesse (NOPA-RCC, Inra,78352 Jouy-en-Josas Cedex, France).

Many animal behaviors are triggered by odor-ant cues from the environment. In particular,macrosmatic animals rely on olfaction to findand choose their food. Besides, the nutritionalstatus is known to modulate the responses of themain output neurons in the olfactory bulb (OB),the mitral cells, and to modify the pleasantnessof food odors. In order to establish a molecular

basis for these observations, we looked for thepresence of orexigenic and anorectic peptidesand their receptors in the first two stages of theolfactory system, the epithelium (OE) and theOB. By immunohistochemistry, RT-PCR andwestern blot analysis, we demonstrate the pres-ence of orexins and their receptors (OXR), lep-tin and its receptors (Ob-R) and insulin recep-tors in both OE and OB. Interestingly, OXRand Ob-Rs are both localised in neurons of theOE, on cilia which express olfactory receptors,and in mitral cells of the OB. In the OE, func-tional studies demonstrate that OXR activationleads to an intracellular calcium rise, via PLCactivation and IP3 synthesis, whereas leptin in-duces the phosphorylation of the transductionfactor Stat3. In the OB, orexins modulate theelectrophysiological responses of mitral cells toolfactory nerve stimulation. Furthermore, in theOE, a number of genes display a modified ex-pression of the nutritional status of rats (fed vs.fasted). Altogether, these results show that pep-tides implied in the regulation of energy home-ostasis are present from the first level of the ol-factory system, and that the nutritional statuscould be detected and integrated at a very pe-ripheral level to finely tune the olfactory mes-sage to the physiology.

Recent data on adipocyte lipid droplets: rela-tionship with the plasma membrane throughcaveolar endocytosis of cholesterol. I. Dugail,S. Le Lay, E. Hajduch, X. Le Lièpvre, C. Thiele,P. Ferré, T. Kurzchalia, K. Simons (InsermU671, Paris, France).

Recent studies on lipid droplets, the specialisedorganelle for lipid storage, have revealed a com-plex structure with a phospholipid/cholesterolmonolayer around a hydrophobic neutral lipidcore. In adipose tissue, these lipid droplets areextremely developed and serve to provide en-ergy from triacylglycerols in case of food de-privation. The adipose tisssue also contains thelargest body pool of free-cholesterol, which ac-cumulates from exogenous sources in the lipiddroplet. Since fat cells are particularly rich incaveolae, which have been implicated in choles-terol transport, we investigated the dynamicsof caveolins in adipocytes and their role in

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cholesterol targeting to lipid droplets. We ob-served that caveolins associated to previouslyformed lipid droplets in 3T3-L1 adipocytes,only in the late stages of adipocyte differenti-ation. Moreover, enlarged lipid droplets fromobese rat adipocytes were enriched in cave-olins. Exogenously added cholesterol inducedthe rapid translocation of caveolins from thecell surface to lipid droplets. The inhibitory ef-fect of a dominant negative mutant of dynamin(dynK44A), the protein kinase C-dependenceof caveolin translocation to lipid droplets, andits modulation by tyrosine kinase inhibitorssuggested that a caveolar endocytic process wasinvolved in this targeting. Caveolin-cholesterolcomplexes on the lipid droplet could be de-tected by immunoprecipitation or by labellingwith a photoactivatable cholesterol analogue.Furthermore, the study of caveolin-1 null miceadipocytes, revealed that caveolin-1 was re-quired to maintain a normal cholesterol contentof adipocyte lipid droplets. These observationsthus identify a new intracellular route for cave-olin between the cell surface of adipoctes andlipid droplets, important for the regulation ofthe free cholesterol content of this organelle.

Effects of learning by familiarisation on thetaste sensitivity to novel foods. A. Faurion,A.M. Pillias, B. Cerf, N. Boireau (NBS-NOPA,Inra, Domaine de Vilvert, Bât. 325, 78352 Jouy-en-Josas, France).

Pure chemicals unknown to subjects were repet-itively tested over weeks in order to assessthe concentration eliciting the same intensityof perception as a reference that the 30 sub-jects had been previously familiarised to. Hedo-nic evaluation, magnitude estimates (M.E.) andfood intake were also recorded. The subjectswere submitted to fMRI prior to any familiari-sation (day 1), after one experimental sessionand after 12–15 sessions. The results showed atremendous decrease of the isointense concen-trations, together with increased M.E., indicat-ing an increased sensitivity with familiarisationto tastants. fMRI showed plasticity through amodification of the number of activated pixelsat the beginning of the familiarisation. Elec-trophysiological recordings of the chorda tym-

pani taste nerve (CT) in 5 groups of 10 ham-sters either drinking water or given the choiceof one tastant versus water for 21 days prior tothe experiment, showed a significant increase ofCT responses to the series of tastants repeated6 times during the experiment in controls, butno increase to the familiarised tastant in thegroup that had been previously familiarised toit. Both peripheral and central levels exhibitplasticity of the quantitative taste response withfamiliarisation.

Subthalamic deep brain stimulation pro-vokes weight gain in Parkinsonian patients.D. Guehl, C. Perlemoine, V. Rigalleau, F.Macia, F. Tison, H. Gin, P. Burbaud (Ser-vice d’Explorations Fonctionnelles du SystèmeNerveux, Hôpital Haut-Lévêque, Av. de Magel-lan, 33600, Pessac, France).

During the course of Parkinson disease (PD),almost half of the patients experience weightloss which may be as much as 10 kg in ap-proximately a quarter of all cases. This weightloss mainly involves the fat mass rather than themuscular mass and is probably due to increasedenergy expenditure (EE). The latter may beraised by motor fluctuations and severity ofmotor symptoms, particularly dyskinesia. Bilat-eral subthalamic (STN) stimulation has provedeffective both on Parkinsonian symptoms andmotor fluctuations in severe forms of PD. How-ever, we had noticed that operated patients gainweight during the first year post-op. We demon-strated that STN stimulation in PD induces asignificant weight gain (WG) of 9.7 ± 7 kg andBMI increase of+ 4.7 kg.m−2 twelve months af-ter surgery. These changes appear to be relatedto a reduction of 16.5% in rest energy expen-diture (REE) without daily energy intake (DEI)adjustment. In comparison to a group of non-operated patients, the reduction in lipid (–27%)and protein (–46%) oxydation induced by STNstimulation could also contribute to WG in ourseries of 19 patients. In addition, we determinedthe acute effects of STN stimulation and lev-odopa on REE and substrate oxidation rate.Switching “on” STN stimulation reduced moreREE (–17.5%) than levodopa (–8.3%). Lipidoxidation was reduced (–24%) by acute STN

Physiology Society Symposium 299

stimulation whereas levodopa reduced glucoseoxidation (–37%) with a slight hyperglycaemiceffect. Since levodopa decreases glucose oxi-dation, the post-op reduction of levodopa dailydose could help prevent the effect of weight gainon glycaemia.

Adipose tissue secretory function and bodyweight regulation. M. Guerre-Millo (U671 In-serm, 15 rue de l’École de Médecine, 75006Paris, France).

It is now recognised that the white adiposetissue (WAT) produces a variety of bioactivepeptides, collectively termed “adipokines”. Al-teration of WAT mass in obesity markedlyaffects adipose secretion. Several adipokinesare overproduced in the obese state and havebeen implicated in obesity-associated compli-cations such as hypertension (angiotensino-gen), impaired fibrinolysis (PAI-1) and insulinresistance (TNFα, IL-6, resistin). Conversely,leptin and adiponectin both exert an insulin-sensitizing effect, at least in part by favoringtissue fatty-acid oxidation through activation ofAMP-activated kinase (AMPK). Besides, leptinand adiponectin have distinct properties. On theone hand, leptin, which is produced in relationto adipose tissue mass, targets the hypothala-mus and allows adapting the rate of food in-take to the level of energy store. Mutations inthe leptin or leptin receptor gene result in hy-perphagia and obesity. These abnormalities arereversed by leptin treatment in leptin-deficientindividuals. However, leptin treatment is inef-ficient in common obesity, which is charac-terised by hyperleptinemia and resistance toleptin. On the other hand, adiponectin exerts apotent anti-atherogenic effect in cellular and ro-dent models of atherosclerosis. In humans, lowadiponectinemia is associated with increasedrisk of cardiovascular diseases. A recent studyrevealed that intracerebroventricular adminis-tration of adiponectin in mice resulted in weightloss. On the contrary to leptin, this effect didnot rely on reduced food intake but rather onincreased oxygen consumption (VO2) and ther-mogenesis. Thus, through its secretory func-tion, WAT lies at the heart of a complex networkof factors capable of influencing several physio-

logical processes, energy homeostasis and bodyweight regulation. Some adipokines, like lep-tin and adiponectin, exert a beneficial effecton energy balance, insulin action and vascula-ture, while the excessive production of otheradipokines could be deleterious in obesity.

Brainstem neuroplasticity and control offood intake. A. Jean, B. Bariohay, C. Char-rier, M. Dallaporta, E. Pecchi, B. Felix, B. Le-brun, J.D. Troadec, E. Moyse (Physiologie Neu-rovégétative, UMR CNRS-Inra-Université PaulCézanne, Faculté des Sciences et Techniques,13397 Marseille Cedex 20, France).

Classically, the neural control of food in-take depends on (i) hypothalamic nuclei whichintegrate adiposity signals, secreted proportion-ally to the fat stores, and (ii) the dorsal va-gal complex (DVC) of the brainstem whichintegrates satiety signals produced in the oro-gastro-intestinal tract during eating to deter-mine meal size. Recent results indicate that theneuroplasticity phenomena within the hypotha-lamus play a role in the mechanisms regulat-ing food intake. The DVC of the adult has alsobeen recently shown to be a site of importantneuroplasticity: (i) the DVC displays high con-tent of PSA-NCAM, GAP-43 and BDNF; (ii) itis a site of neurogenesis; (iii) its glial environ-ment could be a support of the observed neu-rogenesis. We addressed the question whetherbrainstem elements involved in neuroplasticityare also involved in the control of food intake.The results already obtained show that BDNFplays a role as an anorexigenic factor within theDVC: (i) BDNF infusions in the DVC inducedanorexia, weight loss and inhibited swallow-ing, a fundamental motor component of food in-take behaviour; (ii) BDNF protein content wasdown-regulated by fasting and transiently up-regulated by leptin or CCK peripheral treat-ment. Preliminary results show that the DVCglial compartment could also be involved inthe regulation of food intake: (iii) modificationof astrocyte metabolism by methionine sulfox-imide (MSO) decreased food intake and bodyweight; (iv) MSO treatment suppressed the ali-mentary response to 2-deoxyglucose as well asc-fos activation within the DVC. These results

300 Abstracts

indicate that the DVC plays a crucial role in thecontrol of food intake and that the mechanismsinvolved are far to be underlained only by hard-wired reflex circuits.

Session VII. Respiration

Differential kinetics of airway response tohistamine aerosol in central and peripheralairways studied by synchrotron radiation ctimaging in the rabbit. S. Bayat, L. Porra,H. Suhonen, N. Christian, P. Suortti, A.R.A.Sovijärvi (European Synchrotron Radiation Fa-cility, Grenoble, France).

Although airway hyper-reactivity is the hall-mark of bronchial asthma, regional kineticsof airway narrowing are not well understood.We applied a novel CT imaging techniqueusing synchrotron radiation to image stablexenon gas within the airways and peripheral airspaces (Porra et al., J Appl Physiol 2004, 96:1899; Monfraix et al., Phys Med Biol 2005,50: 1) in order to study the kinetics of cen-tral and peripheral airway response to histamineaerosol in healthy anesthetised and mechani-cally ventilated rabbits up to 60 min after his-tamine administration. Individual proximal air-way constriction was assessed by measuringthe luminal Cross-Sectional Area (CSA). Pe-ripheral airway obstruction was estimated bymeasuring the Ventilated Alveolar Area (VAA)following inhaled Xe administration. Overallthoracopulmonary resistance (RLT) was as-sessed continuously. Proximal airway CSA de-creased by 60% of the baseline value in 20 minand recovered gradually by 60 min. The VAAdecreased immediately after histamine inhala-tion by 50% of the baseline value and recov-ered rapidly thereafter. The results indicate sig-nificantly slower airway response and recoveryin central vs. peripheral airways in the rabbit.The kinetics of RLT appeared to be the sum ofcentral and peripheral airway contributions. Inconclusion, we found significant differences inthe kinetics of histamine response in central vs.peripheral airways, as well as differences in air-way reactivity as a function of airway size incentral airways.

Influence of a rehabilitation training pro-gram of “swimming” on ventilatory functionin a young tetraplegic. B. Beaune, J. Perrot,D. Colin (Laboratoire des APS, Université duMaine, Av. Olivier Messiaen, 72085 Le MansCedex 9, France).

The aim of our study was to evaluate theconsequences of a rehabilitation training pro-gram of “swimming” for 5 weeks (1–2 ses-sions per week, 45 min per session) on venti-latory function (tidal (TV), inspiratory reserve(IRV), expiratory reserve (ERV) volumes, vi-tal capacity (VC), forced expiratory volume in1 s (FEV1), maximal expiratory-flow volume(MEFV), time of apnea (TA)) in a male pa-tient, C5-C6 tetraplegic for two years, 17 year-old and without any lung physiotherapy pro-gram. Before training, the patient exhibits astrong ventilatory deficiency, comparable to“pulmonary restrictive syndrome” with normalTV values only (0.7 L). At the end of thetraining program, all volumes and capacitieswere enhanced (IRV: +51%; ERV: +195%; VC:+48%) except TV (–14%). FEV1 and MEFVincreased by 81% and 161%, respectively, andTA rose from 32 to 52 seconds (+63%). Allthese results show that a well-adaptated train-ing program of “swimming” in tetraplegic pa-tient permits successful but partial lung rehabil-itation and allows for benefits compatible withincreased autonomy.

Structure-function relationship in humanbronchial obstruction. P. Berger (Labora-toire de Physiologie Cellulaire Respiratoire,Inserm E356, Université Bordeaux 2, Serviced’Exploration Fonctionnelle Respiratoire,Hôpital Haut-Lévêque, CHU Bordeaux,France).

Airway wall remodeling observed in chronicobstructive pulmonary disease (COPD) con-tributes to alteration in the function of theairways. Air trapping within the peripheral air-ways can be evaluated by lung attenuationmeasurement using quantitative computed to-mography (CT). Airway thickening within theproximal airways can also be evaluated usingCT and a dedicated software tool based on a

Physiology Society Symposium 301

Laplacian of Gaussian algorithm. Such CT datacan thus be compared to both in vitro assess-ment of airway smooth muscle responsivenessand inflammatory cell infiltration and in vivolung function testing measurements. Differentgroups of patients have been included i.e., ex- orcurrent smokers with or without functional ob-struction, and healthy non smoking subjects. Ina first study, we demonstrated that, in smokers,air trapping assessed by the difference betweeninspiratory and expiratory attenuation was cor-related with an inflammatory infiltration of thesmooth muscle layer of small airways. This cellinfiltration involved mainly mast cells and in-creased with the decrease of in vitro relaxationto salbutamol. In a second study, we validatedsoftware for 2D images allowing the assess-ment of different proximal bronchial parametersincluding wall area (WA), internal area (IA).The ratio of the sum of WA to the sum of IA(i.e, ΣWA/ΣIA) which reflected normalised air-way thickening, was significantly different be-tween patients diagnosed with COPD, smokersand control subjects. Normalised airway thick-ening and internal area were significantly re-lated to lung function testing data, includingFEV1, sGaw, FEF25-75. Finally, we developednew 3D software that enabled us to localise air-way remodeling in COPD between the sixth andthe eighth bronchial generation. These workswere funded by PHRC 1997 and 2002.

Assessment of the ventilatory thresholdsfrom heart rate variability in adolescenttriathletes and adult cyclists. F. Cottin, P.M.Leprêtre, P. Lopes, Y. Papelier, C. Médigue,V. Billat (Laboratory of Exercise Physiol-ogy (LEPH), University of Evry, EA 3872,Genopôle, Bd F. Mitterrand, 91025 Evry Cedex,France).

The purpose of this study was to examinewhether it is possible to assess ventilatorythresholds from heart rate variability (HRV)analysis in healthy well-trained subjects. ECG,VO2, VCO2, VE and blood lactate concentra-tion of sixteen well-trained adult cyclists (C,n = 8) and young triathletes (T, n = 8)were collected during an incremental exhaus-tive test performed on a cycloergometer. The

“Short-Term Fourier Transform” analysis wasapplied to RR time series to compute usualHRV components vs. power stages. For all sub-jects, visual examination of both ventilatoryequivalents and instantaneous high-frequency(HF) energy multiplied by the instantaneousfrequency of the HF peak (HF. fHF, HF: 0.15-fmax Hz) vs. time (linked to power stages) hasshown two synchronous abrupt increases, atthe same power level, giving the first ventila-tory threshold (VT1) associated with the firstHF threshold (HFT1), and the second ventila-tory threshold (VT2) associated with the sec-ond HF threshold (HFT2). When expressed as afunction of power, HFT1 and HFT2 were not re-spectively different from VT1 and VT2 in C andT. In addition, HFT1 and HFT2 were respec-tively strongly correlated to VT1 (C: r2 = 0.97,T: r2 = 0.96, P < 0.001) and VT2 (C: r2 = 0.94,T: r2 = 0.97, P < 0.001). The subject char-acteristics and physiological performance lev-els of the two groups in absolute terms wereall significantly different. However, when theperformance values were normalised, no sig-nificant difference was found between cyclistsand triathletes. This study shows that ventila-tory threshold assessment is possible from car-diac RR time series using HRV time-frequencyanalysis in healthy well-trained athletes.

Does the meconial aspiration syndrome af-fect long term pulmonary function? N.Djemal, K. Masmoudi, H. Ben Amar, N. Zouari(Functional Exploration Department, Bour-guiba University Hospital, 3029 Sfax, Tunisia).

Acute pulmonary consequences of the meco-nium aspiration syndrome (MAS) are well de-scribed. However, few studies of the long termpulmonary sequelae in MAS have been made.In order to evaluate long term pulmonary func-tion in MAS survivors, we studied 14 chil-dren aged 4 to 11 years, an average of 7.41 ±2.27 years after injury. Our sample had a meanweight of 24.6 ± 7.35 kg and a mean heightof 124.5 cm ± 10.64. At birth, the mean Ap-gar scores respectively at 1 and 5 min were5.3 ± 2.28 and 7.23 ± 1.74. All 14 chil-dren required oxygen for a mean period of6.35 days ± 4.95. In the current study, the

302 Abstracts

parents answered a questionnaire to evaluateclinical pulmonary and cognitive functions oftheir children. In each child, complete spirom-etry was fulfilled. An exercise stress test onan ergocycle was achieved only by seven chil-dren. Respiratory symptoms such as wheezingepisodes and respiratory tract infections werefound respectively in an average frequencyof 2 ± 1.73 episodes/year and 4.35 ± 3.36episodes/year. Two children had exercise in-tolerance. Spirometry displayed FEV1, Tiffe-neau ratio (FEV1/FVC), TLC and FRC respec-tively in an average of 90.35 ± 1 7.75% th,90.92 ± 5.81% th, 171 ± 64.76% th and 286.5 ±135.96%. The exercise stress test revealed amean VO2max of 90.3% ± 14.56. Spirometry re-alised 5, 10 and 15 min after exercise showed anFEV1 reduction of respectively 8.5, 12.25 and11%. We conclude that children surviving MAShave long term pulmonary sequelae, includingalveolar hyperinflation and airway hyper reac-tivity to exercise.

Antioxidative efficacy of resveratrol againsthepatic damage induced by chronic ethanoladministration in rats. A. Kasdallah-Grissa,B. Mornagui, H. Ben Gharbia, A. Nahdi, N.Gharbi, M. Hammami, S. El-Fazaâ (Laboratoirede Physiologie Animale, Département de Bio-logie, Faculté des Sciences de Tunis, CampusUniversitaire 1060, Tunis, Tunisia).

The chronic consumption of alcoholic bever-ages is a major cause of liver injury and thedevelopment of serious liver disease. Hepato-toxicity of ethanol is well recognised to beassociated with the formation of free radi-cals, lipid peroxidation and oxidative stress.Therefore, the potential role of several an-tioxidant substances such as vitamins andpolyphenols has been investigated in ethanol-induced liver injury. Resveratrol (trans-3,4’,5-trihydroxystilbene) is a naturally occurring phy-toalexin present in grapes and other plantswhich have long been used in traditional ori-ental medicine. It was recently found that thiscompound possesses a variety of biologicalactivities and exhibits antioxidant properties.This prompted us to investigate whether thispolyphenolic compound is capable of exerting

any protective effects in face of chronic ethanol-induced liver damage. Three groups of maleWistar rats were used. The first group servedas controls and received a daily intraperitoneal(i.p.) injection of 0.9% saline. The second groupof rats was treated daily with an i.p. dose of35% ethanol at 3 g.kg−1 body weight. Thethird group of rats was given the same dose ofethanol but allowed a basal diet supplementedwith 5 g.kg−1 resveratrol. Chronic ethanol ad-ministration for 6 weeks produced hepatotox-icity. This was clearly evident by the increase(P < 0.05) in the level of hepatic marker en-zymes such as serum transaminases, alkalinephosphatase and gamma glutamyl transferaselevels. Alcohol administration improved (P <0.01) the formation of malondialdehyde in theliver indicating an enhancement of lipid perox-idation, the major end-point of oxidative dam-age. Drastic alterations were observed in the an-tioxidant defense system, which were reflectedby decreased (P < 0.01) activities of hepatic su-peroxide dismutase and glutathione peroxidase.The addition of resveratrol to the diet of alco-hol treated rats ameliorated the liver function,inhibited the hepatic peroxidation of lipids, andimproved the antioxidant defense system. Thelevels of all these parameters in alcohol treatedrats given a resveratrol supplemented diet werenot different from those of controls. These re-sults demonstrate a potent suppressive effectof resveratrol on hepatic toxicity and oxidativedamage induced by chronic ethanol administra-tion, suggesting a therapeutic potential for thiscompound in liver diseases.

Bronchodilation induced by deep inhalationcorrelates with a decrease in FEV1/FVC dur-ing exercise induced airway obstruction inchildren. F. Marchal, C. Schweitzer, Y. ThiNguyen, Lan Vu Thi Thuy, C. Chone, B. De-moulin (Service d’Explorations FonctionnellesPédiatriques, Hôpital d’Enfants, allée du Mor-van, 54500Vandoeuvre-lés-Nancy, France).

During airway challenge, it has been hypoth-esised that an isolated decrease in FEV1 ex-presses constriction of larger airways while anassociated decrease in FVC relates to closureof smaller airways. A decrease in FEV1/FVC

Physiology Society Symposium 303

should therefore indicate central airway con-traction. A deep inhalation (DI) may relievesmooth muscle constriction in these airways be-cause they are subjected to parenchymal teth-ering. This effect should be reflected in achange in respiratory conductance at 12 Hz(Grs), which more specifically assesses cen-tral airway mechanics. Sixty-two children (7–16 years) with suspected asthma and normalbaseline lung function were studied before and5 min after a free run. FEV1 and FVC wereobtained by spirometry and Grs by the forcedoscillation technique. The Grs response to DI(GrsDI) was calculated as the post- to pre-DIGrs ratio. After exercise, there was a significantdecrease in FEV1, FVC and FEV1/FVC and asignificant increase in GrsDI. A highly signifi-cant correlation was disclosed between the de-crease in FEV1/FVC – but not in FVC – andthe increase in GrsDI (P < 0.0001). The data areconsistent with central airway constriction be-ing a significant component of exercise inducedairway obstruction, reflected by a decrease inFEV1/FVC and relieved by DI.

Physiological effects of 6-month home train-ing, after 10 weeks of institutionalised res-piratory rehabilitation, in COPD patients.J.M. Perruchini, V. Van Wymelbeke, J. Barthe,M. Merati, C. Vassard, L. Jeannin, L. Brondel(A.D.R.RES, 10 rue de Genève, 21000 Dijon,France).

In Chronic Obstructive Pulmonary Disease(COPD) patients, pulmonary Rehabilitation inInstitution (Ri) during a limited period improvesexercise capacity and decreases respiratory dis-tress. When patients come back home, benefitsof Ri are generally lost if home training (Th) isnot pursued. The aim of this study was to evalu-ate the physiological effects in COPD patientsof 10 weeks of Ri, followed by 6 months ofTh. Thirty patients (65 ± 10 years), followed Ri

with 3 sessions.week−1 (50 min cycling, 30 minrespiratory physiotherapy, 45 min quadricepsexercise, 45 min global gymnastics and swim-ming or relaxation). Th was composed of 3 ses-sions/week (50 min cycling and 10 min respi-ratory physiotherapy) under physiotherapy andtechnical assistance. The evaluations consisted

of lung function and exercise testing, measure-ments of walking performance and evaluationof the quality of life. There were no changes inlung function parameters during the whole re-habilitation program. In contrast, some parame-ters related with physical condition or quality oflife increased during Ri, but also during Th, asshown through VO2max, power max, anaerobicthreshold, VE/VCO2, oxygen pulse (VO2/Fc)and total score of quality of life (P < 0.05).During Ri, improvement of life-quality was cor-related with a rise in VO2max (r = 0.426, P <0.05) and VE/VCO2 (r = 0.712, P < 0.05)and during Th it was correlated with a rise inVO2/Fc (r = 0.403, P < 0.05). In conclusion,COPD patients who completed a 6-month pro-gram of Th after 10 weeks of Ri do continueto improve their exercise tolerance and theirlife-quality by an amelioration of cardiovascu-lar function and/or a better muscular extractionof oxygen.

The effect of puberty on lung function inTunisian children. Y. Trabelsi, A. BouchezBuvry, Z. Tabka, N. Gharbi, A. Bienvenue, J.P.Richalet, H. Guenard, A. Zbidi (Department ofPhysiology and lung function testing, SousseFaculty of Medicine, University of Sousse, Av.Mohamed Karoui, 4002 Sousse, Tunisia).

Puberty is one of the most important stepsin life, involving dramatic morphological andphysiological changes. In Tunisian children,nothing is known about the growth of venti-latory function and pubertal stage. The aim ofthe study was to adjust the relationship betweenanthropometric parameters and pubertal stageand to produce reference values for spiromet-ric lung function according to the pubertal sta-tus in Tunisian children. Pulmonary functionvalues were performed with a Minato portablespirometer in 684 healthy Tunisian children(351 males and 333 females) 8–16 years of age.Pubertal status was assessed for males and fe-males according to the Tanner method. In malesand females, height and age were well corre-lated with pubertal stage. Forced vital capac-ity and flow expiratory volume in 1 secondincreased with pubertal stage. Puberty beganand ended earlier in females than in boys.

304 Abstracts

In conclusion, ventilatory function of healthyTunisian school children increases proportion-ally with age, height and pubertal stage. Thisstudy confirmed that lung growth is of shortduration and occurs earlier in females than inmales in the pubertal process. These data areof importance to follow the children suffer-ing from chronic pulmonary diseases duringpuberty.

Session VII. Oxydative stress

Oxidative stress and anaerobic exercise.C. Groussard (Laboratoire de Physiologie etde Biomécanique de l’Exercice Musculaire,UFRAPS Rennes 2, EA 1274, Av. CharlesTillon, Campus la Harpe, CS 24414, 35044Rennes Cedex, France).

Literature data concerning aerobic exercisesand oxidative damages are consistent and havebeen well documented over the last 25 years.It is now well known that the major factor re-sponsible for oxidative damage during aerobicexercise is the increase in oxygen consump-tion. However, many other factors known to in-duce oxidative stress, such as xanthine oxidaseactivation (Mc Cord, 1985), acidosis (Siesjoet al., 1985) and catecholamine autoxidation(Cohen and Heikkila, 1974) might be opera-tive to a greater extent during anaerobic ex-ercise. All these factors lead then to the hy-pothesis that even a non aerobic exercise couldalso induce oxidative stress. However, little at-tention has been directed towards identifying(i) the changes in oxidative stress markers andantioxidants in response to anaerobic exerciseand (ii) the possible sources of reactive oxygenand nitrogen species (RONS) production duringthis type of exercise. The aim of this symposiumis to briefly review the recent publications deal-ing with oxidative stress and anaerobic exerciseand the possible sources of RONS productionduring this type of exercise.

Influence of self low caloric intake and spon-taneous running wheel activity on mitochon-drial free radical production. R. Favier, B.Garait, G. Lacraz, K. Couturier (Fundamental

and Applied Bioenergetics, EMI 221, JosephFourier University, 2280 rue de la Piscine, BP53X -38041, Grenoble Cedex 9, France).

It has previously been shown that both caloricrestriction and chronic exercise are able to mod-ulate mitochondrial free radical generation of-fering a plausible mechanism by which these in-terventions could slow down the rate of aging.In the present study, we evaluated the rate ofhydrogen peroxide (H2O2) production by skele-tal muscle mitochondria isolated from a pe-culiar strain of rats named Lou/C. These ratsare characterised by low energy intake (Cou-turier et al., Int J Obes Relat Metab Disord,2004) and high voluntary running wheel activ-ity (Servais et al., Free Rad Biol Med, 2003).A group of Lou/C rats was chronically exer-cised with running wheels (CEL/C) and com-pared to sedentary Lou/C rats (SedL/C). Inaddition, SedL/C were compared to sedentaryWistar (SedW) rats. Mitochondria were isolatedfrom the quadriceps, and incubated with sub-strates providing reducing equivalents to com-plex I and/or complex II of the mitochondrialelectron transport chain (ETC). MitochondrialH2O2 production was significantly reduced inSedL/C as compared to SedW, a decrease that isnot linked to reduced oxygen flow through themitochondria, but rather to an increased expres-sion of uncoupling proteins (UCP-2, UCP-3)and a reduced activity of complex I of theETC. However, chronic exercise for months didnot enhance H2O2 production by skeletal mus-cle mitochondria. In conclusion, the results ofthis study show that low eater and high run-ner Lou/C rats are particularly suitable for fur-ther study of the mechanisms implicated inthe modulation of mitochondrial free radicalgeneration.

Oral communications

Exercise-induced hypoxemia disappearedduring 24 h cycling in highly trained sub-jects. L. Brondel, D. Callard, J.C. Guilland, D.Moreau, J. Van Hoecke, D. Davenne (Centredes Sciences du Goût, 15 rue Hugues Picardet,21000 Dijon, France).

Physiology Society Symposium 305

Heavy short-term aerobic exercise induces hy-poxemia (EIH) in certain endurance-trainedelite athletes. Nothing is known about hypox-emia evolution during long-term aerobic exer-cise. In order to evaluate this evolution, 9 maleendurance-trained master athletes (age: 38 ±6 years; VO2max 46.5 ± 4.6 mL.min−1.kg−1)and 6 control male subjects (35 ± 8 years;39.0 ± 9.3 mL.min−1.kg−1) participated in thestudy. The 24h-exercise was conducted usingcyclosimulator bicycle trainers. Constant exer-cise power (60.3 ± 4.1% of maximal aerobicspeed) was imposed but interrupted every 4 h by20 min rest periods. Capillary blood gases weredetermined before and 1.5, 5.5, 17.5 and 21.5 hafter the beginning of cycling. Pulmonary ven-tilation, VO2 and non-invasive cardiac output(NICO) were evaluated every 4 h during 10 min.The results show that the “distance covered”was 551.2 ± 36.5 km. EIH was observed 1.5 hafter the beginning of exercise (P < 0.01) butdisappeared later on (P < 0.05): PaO2 valueswere 92.0 ± 7.8 mmHg at rest and 81.3 ± 8.2,85.6 ± 5.0, 91.6 ± 4.1 and 84.8 ± 5.9 mmHgduring exercise. No change in PaO2 was ob-served in control subjects. PaO2 was correlatedwith PaCO2 (r = −871, P < 0.01) and pH(r = −0.838, P < 0.01). The disappearance ofEIH between 1.5 h and 17.5 h was not associ-ated with significant variations in VE, FR, VA,VO2, VCO2, VO2/Fc, NICO, subjects’ tempera-ture but with decreases in P(A-a)O2, pulmonaryshunt, VD, VD/VT (respectively, r = −0.889, r =−0.988, r = −0.902, r = −0.949, P < 0.01) andincreases in VE/VO2, VE/VCO2, (r = 0.928and r = 0.935, P < 0.01). So it appears thatEIH is a transient situation which could be dueto a VA/Q mismatch.

Prognostic value of hematocrit in patientswith severe chronic obstructive pulmonarydisease receiving long term oxygen therapy.A. Chambellan, E. Chailleux, T. Similowski,the ANTADIR Observatory Group (Institut duThorax, CHU Nantes, 44093 Nantes Cedex 1,France).

Although traditionally associated with poly-cythemia, chronic obstructive pulmonary dis-ease (COPD) has a systemic inflammatory com-

ponent that could interfere with erythropoiesis.This study was aimed at describing the distri-bution and prognostic value of hematocrit (Ht)in severe COPD patients prescribed long-termoxygen therapy (LTOT). Two thousand fivehundred and twenty-four patients with COPD,FEV1/VC < 70%, FEV1 < 80% pred, and PaO2

< 7.3 kPa in whom hematocrit (Ht) was avail-able at entry were identified between 1980 and1999 in the French ANTADIR chronic respira-tory insufficiency and home care database (M/F5:1, men 68 ± 10 years, women 70 ± 10). Cor-relation between Ht, demographic data and pul-monary function data were examined. A multi-variate Cox proportional hazard regression wasperformed to identify prognostic factors. MeanHt was 45.9 ± 7.0% in men and 43.9 ± 6.0%in women. Ht was below 39% in 12.6% ofmen and below 36% in 8.2% of women (WHOdefinition of anemia). Ht was negatively cor-related with age (r = −0.245) and FEV1/VC(r = −0.068). It was positively correlated withPaCO2 (r = 0.161) and body mass index (BMI)(r = 0.127). Multivariate analysis found Htas an independent predictor of survival, hospi-tal admission rate, and cumulative duration ofhospitalisation. The 3-years survival was 24%(95%CI 16–33%) when Ht < 35% and 70%(63–76%) when Ht ≥ 55%. In conclusion, lowHt is not uncommon in LTOT-COPD patients.Ht is negatively associated with mortality andmorbidity. Whether the association is causativeor not and whether or not corrective measuresare warranted remain to be determined.

Kinetic distribution of LiveR and muscleglycogen during exercise induced glycogenol-ysis. A. Chaouachi, A. Melançon, D. Massi-cotte, F. Péronnet, C. Lavoie (Centre Nationalde la Médecine et des Sciences du Sport, Tunis,Tunisia).

The objective of the study was to docu-ment the effect of three exercise durations onliver and muscular glycogen distribution withindesmosglycosomes (acid resistant glycosomes)and lyoglycosomes (acid labile glycosomes).Sprague Dawley rats were randomly submit-ted to one of the following groups: rest andswimming exercise: 45, 90 or 180 min. The

306 Abstracts

animals were sacrificed and the rectus femorisand the liver were obtained to measure totalglycogen content as well as glycogen associ-ated with desmo- and lyoglycosomes. In boththe liver and muscle, exercise depleted (P <0.05) total glycogen content and glycogen as-sociated within both glycosomes. The depletionincreased with the duration of exercise. Glyco-gen distribution between desmo- and lyoglyco-somes was 40%: 60% in the liver and 75%: 25%in the muscle in the resting group. These per-centages were modified with exercise durationsin both tissues. In the liver, changes in glycogendistribution were observed after 90 and 180 minof exercise reaching 60% (P < 0.05) and 75%(P < 0.05) in desmoglycosomes, respectively.In the muscle, changes in glycogen distribu-tion were rapidly observed reaching 78% af-ter 45 min, 71% after 90 min and 100% af-ter 180 min (P < 0.05) in desmoglycosomes.During exercise, glycogenolysis was higher inlyoglycosomes than in desmoglycosomes in theliver (P < 0.05). In contrast, in the muscle,glycogenolysis was higher in desmoglycomes(P < 0.05). In conclusion, these results sug-gest that exercise modifies the intracellular dis-tribution of glycogen within desmo- and lyo-glycosomes, and that the contribution to energysupply of the two glycogen subfractions is het-eregenous and different between the muscle andliver, during exercise.

Supported by the Natural Sciences and EngineeringResearch Council of Canada.

Effect of fastskin suits on performance dragand energy cost of swimming. J.C. Chatard,B.D. Wilson (Service de Physiologie Cliniqueet de l’Exercice, CHU St-Étienne, 42 055 St-Étienne Cedex 2, France).

Fastskin Full Body Suits (FB) have beenclaimed by manufacturers to reduce passivedrag by as much as 10% compared to nor-mal suits (N). However, the manufacturer’sclaims have not been backed by published peerreviewed studies. This study was undertakento determine the effect of fastskin suits onswimming performance, drag and energy costof swimming. Fourteen competitive swimmersswam at maximal effort in a 25 m pool for dis-

tances of 25 m, 50 m, 100 m, 200 m, 400 mand 800 m when wearing FB, legs only (L)and N. They performed 4 min swims at their800 m pace when wearing FB, L, and N, inthe swimming flume of the University of Otago,Dunedin NZ. Oxygen consumption was deter-mined using a metabolic cart. Passive drag mea-sures were made when wearing FB, L, and Nat speeds between 1.20 and 2.00 m.s−1. Theorder of all suit and performance conditionswere randomly assigned. The FB and L suitswere purchased from local suppliers and sup-plied to swimmers according to their fit. Therewas a 3.42 ± 0.86% performance benefit (de-creased swim time) for all swimming distanceswhen wearing the FB. The gain was signifi-cantly lower when wearing L (1.93 ± 0.69%,P < 0.01). There was a significant reductionin drag (6.15 ± 7.93% vs. 4.73 ± 4.74) andoxygen cost (5.51 ± 3.01% vs. 4.04 ± 5.54%)when wearing FB and L compared to N. How-ever, the difference between FB and L werenot significant. In conclusion, there appears tobe a performance benefit, and drag and oxygenconsumption reduction when wearing FB and Lcompared to N.

Effect of instruction on the reliability of max-imal voluntary force and maximal rate offorce development during isometric contrac-tion. T. Driss, R. Sahaly, H. Vandewalle, L.Isère, A. Le Pellec-Muller, H. Monod (GPBM,E.A. 2931, UFR STAPS, Université Paris X,200 Av. de la république, 92000 Nanterre,France).

Several studies have shown the importanceof the instruction on maximal voluntary force(MVF) and maximal rate of force develop-ment (MRFD) (Bemben et al., 1990; Christet al., 1993; Sahaly et al., 2001, 2003). MRFDis slower when the subjects are instructed toproduce their “maximal peak force as fast aspossible” than when they are instructed “to fo-cus on MRFD” (Sahaly et al., 2001). The re-liability of isometric strength indices is high(Viitasalo et al., 1980; Bemben et al., 1990;Sleivert et al., 1994; Mirkov et al., 2004). How-ever, the effect of instruction on the reliabilityof explosive force indices has not been studied.

Physiology Society Symposium 307

We compared the reliability of MRFD andMVF measured with Hard-and-Fast instruction(INST 1) vs. Fast instruction (INST2) in 11 menand 12 women. MVF and MRFD were mea-sured in 3 sessions at one week intervals atthe same hour with both protocols. The force-time curve was recorded during unilateral max-imal isometric knee extensions. After familiari-sation, the subjects performed three trials forboth protocols and legs. Reliability was stud-ied by means of ICC and SEE%. ICC of MRFDranged from 0.42 to 0.92 for INST 1 and from0.71 to 0.94 for INST 2. ICC of MVF were sim-ilar for instructions 1 and 2 and ranged from0.91 to 0.99. SEE% of MRFD was higher com-pared to MVF. SEE% of MRFD was lower withINST 2 in both legs and genders. In agreementwith Viitasalo et al. and Sleivert et al., the re-sults of the present study suggest that reliabilityis better for MVF compared to MRFD.

An original method to measure aerobic andanaerobic energy expenditure of in the fieldphysical activities with one high-fixed cam-era. J.P. Eclache, F. Botton (Laboratoire de laPerformance ASTB, 10 rue des Tulipes, 69680Chassieu, France).

In the field energy expenditure (EE) deter-minations often increase actual EE and/orsolely measure aerobic metabolism. This cheapmethod requires four stages. First: the determi-nation of the main fundamental activities FAcharacterised by specific muscular groups andmovements. For each FAl of some seconds du-ration or more, the mechanical variable with themajor statistical weight on EE and an event forend-time are selected, generally speed S and u-turn time; for short event FA such as jumping,shooting, striking, throwing, start, event fre-quency F. Secondly, the experimental subjectsachieve coupled calibrations for each FA or tworepresentative activities FAl and FA consist-ing in an incremental sub-maximal power spe-cific activity, with EE-HR (heart-rate) relation-ship determination in laboratory and S-HR andF-HR relationship in the field. These relation-ships, the physical fitness characteristics andthree orthogonal area references are introducedin a mathematical model which calculates ef-

ficiency functions S-EE and F-EE. Thirdly, avideo recording of the tested activity is achievedwith a high-fixed camera, the coordinates ofwhich are introduced in the software. Fourthly,the time events and the coordinates of the im-age by image tracking of the subject center ofmass are stored and transformed to give real inthe field coordinates, S, F, aerobic and anaer-obic EE of each FA. This method, applied innumerous activities to prepare and drive com-petitions and records, is the only one to furnish,without strain or traumatic risks for the subjects,a good estimation of anaerobic metabolism anda mean of prevention for deleterious activities.

Enlargement of glycogen store in the ratliver and muscle by a sucrose-diet and ex-ercise training. N. El Elj, B. Mornagui, N.Gharbi, S. El Fazâa (Laboratoire de Physiologiedes Agressions, Faculté des Sciences de Tunis,Campus Universitaire, 1060 Tunis, Tunisia).

Glycogen in the liver and skeletal muscle isknown to be important to maintain physical per-formance during prolonged exercise. The pur-pose of this study was to investigate the effectof long-term intake of a sucrose-diet and exer-cise training on glycogen content in the liverand skeletal muscle in male rats. Thirty-tworats (130–150 g) were divided into two dietarygroups and were fed with a control diet or su-crose diet (containing 20% starch) for 4 wk.During this period, one-half of the rats in eachdietary group were trained by swimming ex-ercise (60 min.day−1, 5days.wk−1). The liverglycogen was increased by intake of a sucrose-diet and exercise training (P < 0.5).The glyco-gen content in skeletal muscle showed the sametrend as that in the liver. Glycemia does notchange in all groups. These results indicate thatboth long-term intake of the sucrose diet and ex-ercise training synergistically increased glyco-gen in both tissues.

Normal physical fitness in IDDM adoles-cent girls despite alteration of sympatho-adrenergic response to incremental exercisetesting. E. Heyman, A. Gratas-Delamarche, D.Briard, P. Berthon, S. Vincent, H. Youssef, M.DeKerdanet, P. Delamarche (Laboratoire Phy-siologie Biomécanique Exercice Musculaire,

308 Abstracts

UFRAPS, Université Rennes 2, Av. CharlesTillon, CS 24414, 35044 Rennes, France).

An impaired sympatho-adrenergic response tohypoglycaemic episodes has been described inyoung insulin-dependent diabetic (IDDM) pa-tients, but it is unknown if this altered re-sponse occurs with exercise, and if it could in-fluence physical fitness. In this study, plasmaepinephrine, norepinephrine and glucose weremonitored, via an intravenous catheter, at eachstage of a graded exhaustive exercise in 19 post-menarcheal well-controlled IDDM girls (13.3–18.2 years) and 19 healthy siblings. Exercisetesting allowed to determine peak vo2 andPWC170. Catecholaminergic response was al-tered in the IDDM girls: norepinephrine levelswere significantly depressed at rest and exer-cise while epinephrine levels were significantlyhigher at rest and light workloads (< 84 ±4 W) in the IDDM vs. healthy girls. Plasmaglucose remained stable in the healthy girls,whereas it diminished significantly (–6.2 ±1.3%) throughout exercise in the IDDM girls.However, no relationship was detected betweenthe glucose decrease and the catecholamine in-crease. The altered catecholaminergic responsewas not accompanied by physical fitness im-pairment, since peak heart rate (188.1 ± 2.3vs. 188.0 ± 2.1 bpm), peak VO2 (45.0 ±1.2 vs. 46.2 ± 1.5 mL.min−1.kg lean-body-mass−1) and PWC170 (2.41 ± 0.12 vs. 2.64 ±0.08 W.kg lean-body-mass−1) were similar inthe IDDM and healthy girls. In addition, theregression of heart rate against workload wascomparable in both groups. Nevertheless, theheart rate/norepinephrine ratio was significantlyhigher at rest and during exercise in the IDDMgirls. This study confirms an early sympatho-adrenergic alteration during intense exercise inIDDM girls, but without any implications onphysical fitness or cardiac response. Thus an in-crease in tissue sensitivity to sympathetic drivecould be assumed in young IDDM patients.

Effects of prolonged mechanical ventilationon antioxidant systems in the piglet di-aphragm. S. Jaber, M. Sebbane, C. Koechlin,M. Hayot, X. Capdevilla, J.J. Eledjam, C.Prefaut, M. Ramonatxo, S. Matecki (EA 701,

Laboratoire de Physiologie des Interactions,Muscles et Pathologies Chroniques, 34000Montpellier, France).

Prolonged controlled mechanical ventilation(PCMV) is known to induce diaphragmatic ox-idative stress that seems to be an important fac-tor reducing force generating capacity. In orderto better understand the cellular mechanisms in-volved, the aim of this work was to determinethe effect of PCMV on antioxidant defense inthe diaphragm with a prospective, randomised,controlled animal study. Eleven piglets (15–20 kg) were assigned to one of two groups:a PCMV group (n = 6) ventilated for threedays and a short controlled mechanical venti-lation group (SCMV) (CTR; n = 5) ventilatedfor 3 h. Force frequency curves of the trans-diaphragmatic pressure (Pdi) were obtained invivo by phrenic nerve pacing. Oxidative stresswas evaluated by thiobarbituric reactive sub-stance (TBAR) content and the enzymatic an-tioxidant activity of both superoxide dismu-tase (SOD) and glutathione peroxidase (GPx)in samples of diaphragm. Pdi decreased in thePCMV group by 30–35% over the three days atall frequencies. Diaphragm TBAR content wassignificantly higher and SOD activity was lowerin PCMV animals than in control animals after72 h. GPx activity tended to be lower in the di-aphragms of PCMV animals, but this differencewas not significant. This study shows that threedays of MV in piglets is associated with a de-crease in antioxidant activity which could em-phasise oxidative stress and both contribute tothe diaphragm dysfunction caused by MV.

Effect of prior heavy intensity exercise onthe phase II VO2 kinetics after training. A.Marles, R. Legrand, N. Blondel, P. Mucci, S.Perrey, F. Prieur (Laboratoire d’Analyse Mul-tidisciplinaire des Pratiques Sportives, Univer-sité d’Artois UFRSTAPS de Liévin, chemin duMarquage, 62800 Liévin, France).

It has been shown that metabolic acidosis atthe onset of exercise can speed VO2 kineticsby a greater O2 availability (due to acidosis-induced vasodilatation and the Bohr effect).The aim of this experimentation was to eval-uate (1) whether training induced a reduction

Physiology Society Symposium 309

of lactic acidosis at the onset of a heavy exer-cise preceded by heavy-intensity warm up and(2) if this reduction affected the phase II VO2

kinetics. Eleven sedentary subjects performedtests on a cycle ergometer before and after six-weeks of interval training at 120% VO2max. Thetest was composed of two 6-min bouts of con-stant work rate exercises (at 50% ∆ ventilatorythreshold –VO2max) separated by 6 min at 35 W.This test was performed twice and data wereaveraged and fitted. The time constant (τ) ofthe phase II VO2 kinetics during the first boutwas not altered by training (pre-training: 27.2 ±6.7 vs. post-training: 23.6 ± 9.0 s; NS). Train-ing significantly diminished the blood lactateaccumulation at the onset of the second bout(pre-training: 6.2 ± 1.9 vs. post-training: 4.2 ±1.8 mmol.L−1; P = 0.01) while τ of the phase IIVO2 kinetics of the second bout was not signifi-cantly affected by training (pre-training: 26.0 ±5.4 vs. post-training: 26.6 ± 5.9 s; NS). In con-clusion, τ of the second bout was not longerafter training while blood lactate accumulationwas decreased, this may suggest that metabolicacidosis did not influence the phase II VO2 ki-netics. However, this unchanged VO2 kineticsmay be due to not important enough residualeffects with training on local vasodilatator tomodulate O2 delivery.

Influence of pattern life on the results of six-minute walk test. K. Masmoudi, S. Aouicha,H. Fki, M. Ketata, N. Zouari (Functional Explo-ration Department, Bourguiba University Hos-pital, 3029 Sfax, Tunisia).

To study the effect of socio-economic condi-tions, educational level and physical activity de-gree on the results of the six-minute walk test(6 min WT). One hundred fifteen-five volun-tary normal subjects (75 female) aged 54.95 ±0.87 years were studied. Anthropometric andpattern life parameters of each subject werenoted. Two 6 min WT were carried out succes-sively with a 30 min interval between them ina hospital corridor on a way of 30 m length inthe afternoon. American Thoracic Society rec-ommendations were respected. The parametersstudied during 6 min WT were distance cov-ered, heart rate as well as dyspnoea level eval-

uated by the analogical visual scale. The dis-tance covered was better at the second 6 minWT for all subjects (509 ± 83 m vs. 542.7 ±89.6 m; P < 0.001). Significant correlationswere found between distance covered (m) andsex ( M: 584(3); F: 498(3); P < 0.001), age(r = −0.47; P < 0.001), IMC (r = −0.40;P < 0.001), origin (urban: 566.2 ± 9; rural:513.5 ± 10; P < 0.001), education level (il-literate: 483.1 ± 9, primary: 572.7 ± 9, sec-ondary: 600.9 ± 16.3; superior: 638.3 ± 17.6;P < 0.001) and physical activity degree (weak:454.9 ± 8, average: 550.1 ± 7, high: 633.5 ±9; P < 0.001). In conclusion, living conditionsmust be taken into account when interpretatingthe 6 min WT.

Effect of a low exercise intensity on mdxhindlimb muscle. S. Matecki, J. Gayraud,A. Cochen, K. Lamber, C. Koechlin, M.Ramonatxo (EA 701, Laboratoire de Physiolo-gie des Interactions, Muscles et PathologiesChroniques, 34000 Montpellier, France).

Dystrophic muscle training induces beneficialand deleterious effects according to exerciseintensity with unknown cellular mechanisms.The aim of the study was to assess the ef-fects of voluntary wheel running exercise on(a) in vivo contractile properties, (b) enzymaticactivities and (c) oxidative stress on the tib-ialis anterior of the mdx mouse, a model ofDuchenne muscular dystrophy (DMD). Eigh-teen mice, aged 8 months old, were randomisedinto two groups. The training group had free ac-cess to voluntary wheel running for 6 weeks.The control group was maintained in a reducedarea and was considered as sedentary mice. Thetibialis anterior of trained mdx mice showedhigher maximal tetanic tension (71.4 ± 4.2 vs.59.5 ± 3.7 g, P < 0.05) and higher specifictension (12.2 ± 0.06 vs. 10.5 ± 0.09 N.cm−2,P < 0.05) in vivo than sedentary mice in vivo.However, exercise had no effect on the fati-gability of the muscle. Moreover, The activ-ity of citrate synthase (24.0 ± 0.4 vs. 24.4 ±0.4 µmol.mn−1.g−1) and lactate dehydrogenase(403 ± 32 vs. 404 ± 17 µmol.mn−1.g−1) wasunchanged. Lipid peroxidation evaluated bymalondialdehyde concentration (MDA), which

310 Abstracts

is an indirect index of oxidative stress was in-creased in the training group (131 ± 10 vs. 94 ±3 µmol.g−1, P < 0.05) compared to the controlgroup. The activity of glutathion peroxidase, anantioxidant enzyme, did not change after exer-cise (7.09 ± 0.7 vs. 5.9 ± 0.3 µmol.mn−1.g−1).In conclusion, low intensity exercise induced inthe tibialis anterior of mdx mice, a beneficial ef-fect on force production in spite of any changein fatigue resistance or oxidative metabolismand an increase in oxidative stress.

Prevalence of exercise-induced broncho-spasm in basketball players in a hot/humidenvironment. F. Messan, J. Lounana, J. Medelli(Unité de Biologie de l’Effort et de Médecinedu Sport, CHU Amiens, place Victor Pauchet,80054 Amiens Cedex 1, France).

Several studies have shown that exercise-induced bronchospasm (EIB) is higher amongwinter sport athletes. Thus, dry, cold air is thestrongest triggering mechanism of EIB. To in-vestigate whether regular training in a tropi-cal climate (ambient temperature 26 ◦C–39 ◦C;relative humidity 38%–80%) has a possibleeffect on EIB, we studied 20 young 19.3 ±1.59-year-old basketball players in Cotonou(Benin). A questionnaire evaluated asthma his-tory and common symptoms of EIB. A cal-ibrated portable spirometer Pony Graphic�

(Cosmed, Italy) was used on the field to assesslung function. Spirometry was performed at restand 5, 10, 15, 20 and 25 min after a specificexercise. Then, an ethnic correction factor wasapplied to all spirometry data. A fall in FEV1

of at least 11% was used to evaluate EIB+ andathletes who did not meet this criterion weregrouped as EIB−. No significant difference wasnoticed between groups concerning anthropo-metric, training data and predictive values. Clin-ical symptoms were reported in 12/20 subjects(60%) and EIB+ in 7/20 (37%). This last valueis much higher than the one of the general pop-ulation (4%–20%). None of the EIB+ group’svalue matched with ATS/ERS asthma criteria atrest. Postexercise variation from the baseline inFVC, FEV1 and PEF were significantly differ-ent between EIB− and EIB+ respectively: 15 ±17% vs. 18 ± 10%, (P = 0.001); 13 ± 16% vs.

17 ± 6%, (P = 0.003) and 7 ± 17% vs. 11 ±9%, (P = 0.023). FEV1/FVC, FEF25-75 andMEF25 were not different. This study showsthat EIB is also induced in hot/humid condi-tions and its prevalence is the same as the onedescribed in other studies carried out in conti-nental climates.

Effect of mode of recovery on the perfor-mance after supra-maximal intermittent ex-ercises. I. Miladi, A. Temfemo, S. Manden-gué, S. Ahmaidi (EA 3300: APS et ConduitesMotrices: Adaptations-Réadaptations, Facultédes Sciences du Sport, 80025 Amiens, France).

The efficiency of the recovery mode is currentlya butt of criticism for it could vary the per-formance after the intermittent efforts. Never-theless, stretching turns out to contribute to abetter muscular elasticity and blood irrigation,which could also influence recovery. The aimof this study was to determine the effect of themode of recovery on performance after supra-maximal intermittent exercises. Nine subjectstook part in this study. They made three coursesof intermittent exercises using three randomisedmodes of recovery: passive (RP), active (RA)and stretching (RS). The intermittent test con-sisted in doing two series of four repetitions at120% MAP during 30 s alternated with a 30-srest period. The mode of recovery was modi-fied between the 4 min series. After the secondseries and the 4 min of recovery, the subjectsperformed a Tlim (maximum time) at 120%MAP until exhaustion. The VO2 and the FCwere recorded by a K4b2. The results demon-strate that the longer length of the Tlim wasobtained after an RS (P < 0.05) but no differ-ence compared with RA. An increase of peakFC and VO2 in both series was observed. How-ever, a significant difference in VO2 peak wasfound between RA and RP (P < 0.05) as wellas RS and RP. Besides, the VO2 peak devel-oped during RS was lower compared to RAand RP, though a longer Tlim was performedduring RS. This could be explained by an in-crease in the nervous activity (EMG) of themuscle and an important lactate eliminationduring RS. However, no significant differencewas observed in VO2 peak during Tlim.

Physiology Society Symposium 311

Muscle oxygenation and blood volume dur-ing the Wingate anaerobic test.W. Moalla, G.Dupont, S. Berthoin, S. Ahmaidi (Faculté desSciences du Sport, 800250 Amiens, France).

The purpose of this investigation was to studythe time course of near infrared spectroscopy(Nirs) parameters during a 30-s Wingate anaer-obic test (WAnT). Twelve male subjects (24.4 ±3.9 years; 175.6 ± 6.4 cm; 71.2 ± 6.9 kg;and 16.3 ± 4.1% fat) performed a 30-s WAnTon a cycle ergometer (Monark 814E, Swe-den). Peak power, mean power and fatigue in-dex (FI) were calculated. Blood lactate con-centration [La] was determined 3-min after thetest. Respiratory gas exchanges were measuredbreath-by-breath using a K4b2 device. Muscleoxygenation (MO2) and blood volume (BV)were assessed continuously by Nirs (Runman,USA) on the vastus lateralis muscle. An arte-rial occlusion was applied immediately at theend of the test to determine changes in MO2.Mean peak power, mean power and an FI were850 ± 129 W, 644 ± 73 W and 46.7 ± 17.3%,respectively. VO2peak measured at the end ofthe WAnT was 46.1 ± 6.2 mL.min−1.kg−1. Nochanges in BV were found between resting andend exercise values. MO2 decreased progres-sively and significantly from the beginning untilthe end of the 30-s WAnT (P < 0.01). The de-cline rate of oxygenation calculated was 0.89 ±0.23%/s. The latter was significantly related tothe VO2peak (r2 = 0.86, P < 0.001). In contrast,no significant relationship was found neither be-tween MO2 and FI nor between MO2 and per-formance (peak and mean power). These resultsindicate that BV was not affected during supra-maximal exercise and that muscles use oxygenstore from the beginning even during anaero-bic exercise. Finally, peripheral muscle oxygenconsumption measured by Nirs reflect systemicoxygen uptake.

Exercise ventilatory constraints in pre-pubescent trained children. C. Nourry, F.Deruelle, C. Fabre, G. Baquet, F. Bart, J.M.Grosbois, S. Berthoin, P. Mucci (Labora-toire d’Analyse Multidisciplinaire des PratiquesSportives, Université d’Artois, chemin du Mar-quage, 62800 Liévin, France).

We studied mechanical ventilatory constraintsin 13 endurance-trained (Tr) and 11 untrained(UT) prepubescent children by plotting the ex-ercise flow-volume (FV) loops within the max-imal FV loop (MFVL) measured at rest. TheMFVL allowed to determine forced vital ca-pacity (FVC) and maximal expiratory flows.Expiratory and inspiratory reserve volumes rel-ative to FVC (ERV/FVC and IRV/FVC respec-tively) were measured during a progressive ex-ercise test until exhaustion. Breathing reserve(BR) and expiratory flow limitation (expFL),expressed in the percentage of VT and de-fined as the part of the tidal breath meeting theboundary of the MFVL, were measured. HigherFVC and maximal expiratory flows were foundin Tr than UT (P < 0.05) at rest. Our re-sults have shown that during exercise, exceptin one subject, all Tr regulated their VT withinFVC similarly during exercise, by breathingwith low lung volume at the beginning of exer-cise followed by breathing with high lung vol-ume at strenuous exercise. In UT, the breathingpattern was quite heterogeneous. The propor-tion of children who presented an expFL wasnearly the same in both groups (∼ 70% witha range of 14% to 65% of VT) and no sig-nificant difference was found during exerciseconcerning expFL. However, higher ventilation(VE), ERV/FVC and dyspnea associated withlower BR, IRV/FVC and SaO2 were reportedat Ppeak in Tr than UT (P < 0.05). These re-sults suggest that, because of their higher VE

level, trained children presented higher ventila-tory constraints than untrained children. Thesemay negatively influence the SaO2 level anddyspnea during strenuous exercise.

Effect of gender, exercise intensity andexercise duration on lipid oxidation dur-ing exercise in overweight subjects. F. Pil-lard, E. Garrigue, C. Moro, I. Harant, I. DeGlisezinski, F. Crampes, D. Rivière (Serviced’Exploration de la Fonction Respiratoire et deMédecine du Sport, Hôpital Larrey, 24 cheminde Pouvourville, TSA 30030, 31059 ToulouseCedex 9, France).

To determine if there is a gender difference inlipid oxidation with exercise and the optimal

312 Abstracts

exercise intensity to oxidize a larger amountof lipids in overweight subjects. Nine youthhealthy overweight male and 9 healthy over-weight females were selected (BMI: 27.9 ± 0.4vs. 27.2 ± 0.5 respectively; ns). On one day, thesubjects first performed a 30 min cycling exer-cise at 30% VO2max (E1-session) followed by a30 min exercise at 50% VO2max (E2-session). Ina second session, they performed a similar E1-session followed by 30 min at 70% VO2max (E3-session). From the gas exchange measurements,the nonprotein Respiratory Quotient (RQ) andthe debit of fatty acids mg oxidised.min−1.kg−1

lean mass (FAOD/kgLM) were calculated. Plas-matic concentrations (pc) of glycerol and non-esterified fatty acids (NEFA) were assayed. RQwas significantly lower for women only dur-ing the E1-session. For both genders, RQ de-creased with the duration of exercise duringE2 and E3-sessions. During the E1-session, theFAOD/kgLM was higher among women and itdid not change over time despite the pcNEFAbeing increased. FAOD/kg LM was higher dur-ing the E2-exercise. During E2 and E3-sessions,the FAOD/kgLM was increased as the exercisetime was prolonged (over 10 and 20 min) simul-taneously with the increasing of the pcNEFA.In conclusion, lipid oxidation during exerciseis optimised for middle-intensity exercise andlong exercise. The lack of lipid mobilizationwould be an essential factor that would limitlipid oxidation in middle and high-intensity ex-ercises.

Effect of prior heavy exercise on pulmonaryO2 uptake and muscle oxygenation. F. Prieur,A. Marles, R. Legrand, N. Blondel, P. Mucci(Laboratoire d’Analyse Multidisciplinaire desPratiques Sportives, UFR STAPS, chemin duMarquage, 62800 Liévin, France).

Purpose: pulmonary O2 uptake (VO2) and mus-cle oxygenation were examined during twobouts of heavy cycling exercise in younghealthy subjects. Methods: ten young malesperformed two constant work rate exercises ofsix minutes (at 50% ∆ ventilatory threshold –VO2max) separated by 6 min at 35 W. VO2 wasmeasured breath by breath and muscle oxygena-tion of the right vastus lateralis was monitored

by NIRS and was expressed in % accordingto the ischemia-hyperemia scale (Muscle oxy-genation = Mox%). The changes in VO2 (i.e.the VO2 slow component) and in Mox% dur-ing each bout were evaluated as the differencebetween the 6th and the 3rd minute of exer-cise (∆VO2(6′−3′) and ∆Mox(6′−3′)). Results: VO2

was not different at the end of each bout of ex-ercise (bout 1: 2320 ± 339 mL.min−1 vs. bout2: 2316 ± 371 mL.min−1, NS ) and Mox% wassignificantly higher at the end of the secondbout (31.1 ± 6.3%) in comparison with the firstone (24.8 ± 6.5%, P < 0.001). ∆VO2(6′−3′) wassignificantly reduced by prior exercise (187 ±66 ml.min−1 vs. 94 ± 69 mL.min−1, P < 0.001)whereas ∆Mox(6′−3′) was not significantly al-tered by prior exercise (bout 1: –0.7 ± 2.9%vs. bout 2: –1.1 ± 1.5%, NS). Conclusion: mus-cle oxygenation at the end of heavy exercisewas enhanced by prior heavy exercise suggest-ing that muscle O2 delivery was improved bya vasodilator-induced acidosis effect. Moreover,this study does not support the hypothesis thatthe VO2 slow component is associated withchanges in muscle oxygenation during exercisesince prior exercise decreased ∆VO2(6′−3′) butdid not alter ∆Mox(6′−3′).

SaO2 is normalised during aerobic exer-cise in hypoxemic obese adolescents. J.M.Sène, M.L. Frelut, G. Pérès (Physiologie duSport, CHU Pitié-Salpètrière, AP-HP75013Paris, CTP Margency et Hôpital St-Vincent-de-Paul AP-HP 75014, Paris, France).

Aerobic conditions are very important to main-tain and improve during physical training inobese subjects. Blood oxygen saturation (SaO2)was measured during an aerobic exercise per-formed in agreement with current recom-mended physical activities for obese adoles-cents. SaO2 was measured on arterialised blood(GEM Premier 3000� analyser) in 19 sedentaryobese (38.5 ± 5.4 kg.m−2) adolescents (13.9 ±1.5 y) during a rectangular exercise performedon a cycle ergometer (Monark 824E�). The testincluded 4 successive phases: T1 at rest (5 min),T2 at 50% VO2max (10 min), T3 at 70% VO2max

and T4 at recovery (5 min). Expired gases wereanalysed (Schiller-Medisoft�) and heart rate

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was recorded (Polar�). SaO2 increased signif-icantly during exercise between T1 (93.7% ±1.6) and T2 (95.3% ± 1) or T3 (94.9% ± 1.3)and remained stable at T4 (94.8% ± 1.5). Thesevariations are fitting corresponding changes inPaO2 at T1 (65 ± 6 mmHg), T2 (74 ± 5 mmHg),T3 (77 ± 6 mmHg) and T4 (74 ± 8 mmHg).The ventilatory stimulation obtained by stim-ulation of exercise leads to a significant (P <0.01) increase in SaO2 and PaO2, reflectingimproved alveolar ventilation. In conclusion,Well-designed rectangular aerobic exercise isable to restore better oxygen flow in obese ado-lescents.

Contribution of oxidative stress in unloaded–induced skeletal muscle atrophy: preventionby vitamin E supplementation. S. Servais,R. Favier, M.H. Mayet-Sornay, C. Duchamp,D. Desplanches (Unité Mixte Recherche 5123CNRS, Université Claude-Bernard, Lyon,France).

Exposure to reduced activity induces skeletalmuscle atrophy. Oxidative stress might triggermuscle wasting. This study was designed to testthe hypothesis that long-term supplementationof the lipid-soluble antioxydant vitamin E priorand during the phase of unloading would coun-teract some of the detrimental consequences inrat soleus muscle. Fourteen days of hindlimbsuspension caused a 50% atrophy while withvitamin E the soleus muscle atrophied only by32%. After suspension, administration of vi-tamin E partly prevented the loss of type I(–59% vs. –38% for H rats) and IIa (–42%vs. –32% for H rats) fibre size. Supplementa-tion affected neither the decreased ratio of re-duced (GSH) vs. oxidised glutathione (GSSG)nor the increased antioxydant enzyme (super-oxide dismutase, catalase, glutathione perox-idase) activities observed after unloading. Incontrast, vitamin E resulted in increased levelsof UCP2 (uncoupling protein) and HSP 72 (heatshock protein) as a complementary protectionagainst oxidative stress and suppressed the in-crease (+50%) in concentrations of thiobarbi-turic acid-reactive substance (TBARS) causedby suspension. Our results suggest that oxida-tive stress contributes to soleus atrophy and vi-

tamin E supplementation partly prevents muscledisuse.

Alteration of the mitochondrial efficiency innon-alcoholic steatohepatitis: a liver adapta-tion? B. Sibille, C. Romestaing, V. Rouleau,M. Dautresme, I. Ollivier, M. Belouze, B. Rey,S. Servais, C. Duchamp, M.A. Piquet (PICM,UMR5123 CNRS-UCB Lyon 1, France).

The non alcoholic steatohepatitis (NASH) isan emerging pathology associated with obesityand insulin resistance. The causes of NASHand its consequences on liver functions arepoorly understood. The aim of this study wasto evaluate the modifications of mitochondrialmetabolism in rats fed a choline-methionine de-ficient diet (CMDD), a known model of NASH.Male Wistar rats fed a standard diet or CMDDduring 6 weeks. Liver mitochondria respirationand efficiency (ATP/O) were measured. Reac-tive oxygen species (ROS) production was es-timated using a fluorimetric detection of mi-tochondrial H2O2 formation. Lipid metabolismwas approached by a measure of ketone bodyproduction and oxygen consumption of isolatedhepatocytes from fasted rats. Liver triglyceridecontent (30-fold increase) and histologic analy-sis confirmed the steatohepatitis in CMDD rats.An uncoupling of the mitochondrial oxidativephosphorylation in CMDD fed rats was demon-strated by an enhanced oligomycin-insensitiverespiration (32.2 ± 2.1 vs. 20.0 ± 1.3 nanoatomO/min/mg protein, P < 0.05), a decreased mi-tochondrial efficiency and a reduced ROS pro-duction (5.6 ± 2.7 vs. 19.2 ± 4.2 pmolesH2O2/nmoles O2, P < 0.05). These results wererelated to an enhanced (56%) activity of the cy-tochrome oxidase. An increased lipid oxidationwas found in CMDD fed rats as reflected byboth a rise in the following: (i) isolated hep-atocyte respiration with dihydroxyacetone andoctanoate (38.9 ± 4.2 vs. 27.2 ± 2.6 µmolesO2/unit of citrate synthase) and (ii) ketone bodyformation (178 ± 19 vs. 139 ± 9 µmoles/unitof citrate synthase). In conclusion, choline-methionine deficient diet fed rats showed amitochondrial dysfunction suggesting a liveradaptation to the overload of triglycerides andoxidative stress. Indeed, mitochondrial uncou-pling increased lipid oxidation and decreased

314 Abstracts

ROS production. These mitochondrial adapta-tions could limit NASH-associated injuries.

Effect of endurance exercise on airway cellsin runners. Z. Tabka, W. Ben Turkia, I. BenCheikh, B. Sriha, A. Zbid, (Service de physiolo-gie et des Explorations Fonctionnelles, HôpitalFarhat Hached, Sousse 4000, Tunisia).

Recent studies have shown that asthma is mostcommonly found in endurance events, such ascycling, swimming, or long distance-running.There is a high prevalence of asthma and exer-cise induced bronchoconstriction. A long termeffort and resistance in athletes is often asso-ciated with symptoms and signs of airway in-flammation. The use of induced sputum is aconvenient and reliable non-invasive method ofassessing airway inflammatory cells. The pur-pose of this study was to investigate the effectof endurance exercise on total and differentialairway cell counts. Ten long-distance runners(19 ± 3 years) and 12 control subjects (20 ±3 years) were studied. Pulmonary function testswere performed using spirometry. Sputum wasinduced on two occasions using nebulised hy-pertonic saline (10%), before and after one hourrunning at 80% of VO2max. Analysis of inducedsputum showed increased cellularity (P < 0.01)after the race. Instead the absence of post-racerespiratory symptoms or spirometric changes,airway cell counts change significantly: the run-ners showed increased neutrophil and lympho-cyte differential counts in induced sputum (P <0.02). Physical exertion, particularly when in-tense and prolonged, causes significant stress tothe respiratory system. Associated hyperventi-lation and increased airway exposure to con-taminants of inhaled air could explain cellu-lar changes. This study shows an increase inthe airway of inflammatory cells, which reflectsonly a normal response to a supra-physiologicstimulus.

Reduction in spontaneous physical activitylevel in daily life: possible role in humanoverweightness. V. Van Wymelbeke, V. Gigot,L. Nataf, D. Rigaud, L. Brondel (Centre desSciences du Goût, 15 rue Hugues Picardet,21000 Dijon, France).

The prevalence of overweightness in most af-fluent countries has increased in recent yearsand the reduction of physical activity level indaily life could play a major role in this phe-nomenon. In order to check this hypothesis,24 men (25.2 ± 1.3 years) differing in their bodymass index (lean: 19.2 ± 0.3 kg.m−2, normal:22.5 ± 0.6 kg.m−2, heavy: 28.7 ± 0.6 kg.m−2)and in their food intake (little eaters: 7361 ±397 kJ, normal eaters: 9919 ± 242 kJ, big eaters:12615 ± 731 kJ) were recruited. Food intakeswere evaluated by a 7-d food record and con-trolled during 2 days before the 24 h-session ina calorimetric chamber. Energy expenditure andspontaneous physical activity were measuredrespectively by indirect calorimetry and by aforce plate-form coupled with an accelerome-ter. The results indicate no difference in energyintakes between the 3 weight groups. Physi-cal activity measured by the force platform islower and with less variability (SD of accel-erations) in the heavy group than in the leangroup (r = −0.445, P < 0.05). Furthermore,lean and big eater subjects have a greater spon-taneous physical activity than heavy and littleeater ones (r = −0.410, P < 0.05). In con-clusion, this study shows that overweight sub-jects have a limited spontaneous physical ac-tivity (qualitatively and quantitatively) in dailylife. Overweight and lean individuals could be-have differently; sedentary behaviour could befavoured by overweight subjects.

Oxidative stress and biochemical evolutionof professional cyclists during different racetypes. I. Vouldoukis, G. Peres, G. Guillaume,D. Mazier, M. Conti (Inserm/UMR 511, CHUPitié Salpétrière, AP-HP, Université Paris VI,75013 Paris, France).

The aim of this work was to evaluate biochem-ical and oxidative stress evolution among pro-fessional cyclists during intensive exercise. Inthis way, we chose two different race types, ashort and individual against the clock race (A)and a heavy endurance team race (B). Elevenblood parameters allowing oxidative stressexploration and 23 metabolical parameters werefollowed before and after exercise. The resultswere strongly different between race type, but

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also between racers. During the (A) race, an al-teration of antioxidant defences was observed,with an increase in MDA, oxidised glutathionconcentrations and glucose-6-phosphate deshy-drogenase activity. A strong hyperlactatemiawas observed, with a decrease in bicarbon-ate concentration. Racers implemented their li-pidic metabolism, with an intensive lipolysisand induction of ketone bodies. During the(B) race, more pronounced variations of an-tioxidant defences were observed, like modifi-cations in G6PDH, Cu/Zn SOD, catalase andglutathione reductase activities. Discrete lipol-ysis was observed – but no ketone mobilisation– and signs of muscular lysis and electrolyticperturbations. However, the biochemical statusdiffered between the racers, with great inter-individual variations and adverse evolutions. Inthe two types of races, the racers with the bestresults had the best antioxidant status beforeraces. Moreover, during the (A) race, the bestracer did not implement lipidic metabolism. Inconclusion, at the end of intensive exercise, an-tioxidant and biochemical status of professionalcyclists depends on the type of race, individualand short, or long and intensive. The initial sta-tus seems to be of the major importance to en-sure performances.

Obesity among Lebanese adolescents: behav-ioral factors (physical activity and dietaryhabits). H. Youssef, C. Jacob, E. Moussa, M.Zind, C. Groussard, A. Delamarche (Labora-toire de Physiologie et de Biomécanique de laPerformance Motrice, Université de Balamand,El- Koura, Nord Liban, PO Box, 100 Tripoli,Liban).

Currently, the prevalence of obesity and its re-lated diseases are increasing all over the worldand especially in industrialised and develop-ing countries. The latest studies show that thisblight is affecting the young population moreand more. Lebanon is no exception, it hasa growing number of obese and overweightyoung adolescents. Indeed, Sibaï et al. (2003)reveal that 7.7% of boys and 2.9% of girls agedbetween 10 and 19 years are obese, and 26.9%and 14.7% of them are overweight. These per-centages become reversed at an adult age: fe-

males (18.8%), males (14.3%). However, theseauthors did not explain this paradox. Therefore,the objective of this study was to carry out a sur-vey during adolescence which is a key periodconcerning morphological changes. Seven hun-dred forty-five Lebanese adolescents (14–18 y)participated in this study (420 girls, 315 boys).The first results confirmed those of Sibaï et al.(2003) since we reported more obese and over-weight subjects in boys compared to girls (9.5%vs. 1.9%) and (22.5% vs. 13.1%). Concerningthe behavioral aspect, on the contrary to moreindustrialised countries, Lebanese overweightand obese boys and girls are more interested inextracurricular physical activities than healthysubjects (in boys: 58.5% vs. 27.5% and in girls:38.1% vs. 27.5%). However, only 37% of boysand 25.5% of girls questioned, declare that theyhave breakfast everyday. Therefore, more inves-tigations are needed in their dietary habits insearch of reasons for obesity.

Effects of swallowing on central respiratorypattern generator. F. Al Chama, P. Calabrese,G. Benchetrit, P. Baconnier (TIMC-PRETA,Faculté de Médecine de Grenoble, UJF, BP 53,38041 Grenoble Cedex 9, France).

In order to characterise the interaction betweenrespiration and swallowing and its eventual dys-functions, we recorded ventilation on 4 healthysubjects (age 25–30, 2 males) during periodswith spontaneous (saliva) or provoked (bev-erage) swallowing. Respiratory signals wereobtained by respiratory inductance plethysmog-raphy such this is the only measure compati-ble with drinking and eating. Each swallowingwas characterised by its duration and time ofoccurrence in the respiratory cycle. The effectof swallowing on the respiratory pattern wasquantified by the changes induced in the cur-rent cycle duration and amplitude, and in theamplitude and inspiratory and expiratory dura-tions of the following cycle. The recorded swal-lows can be grouped into three categories thosewhich (i) start and end during inspiration, (ii)start and end during expiration and (iii) start ininspiration and end in expiration. The resultsshow the following (i) the duration of swal-lowing is simply added to the cycle duration

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as compared to the preceding cycle and (ii)with regards to the following cycle, the laterthe swallowing occurs in the cycle the largerthe increase in its amplitude. We developeda mathematical model describing the interac-tion between the central respiratory pattern gen-erator and the mechanical respiratory system,which allows testing the hypothesis that dur-ing swallowing, the respiratory centers progressis stopped. An additional hypothesis necessaryto explain the increase in the following cycle’samplitude is that during simulated swallowing,the central respiratory pattern generator is pro-gressively moved away from its free-run cyclictrajectory. The three types of observed swallow-ing, were simulated with our model and the re-sult shows that the model behaves qualitatively(and often quantitatively) similarly to the phys-iological system.

Effects of fasting at Ramadan on exercisesubstrate utilisation and insulin sensitivity. I.Aloulou, K. Masmoudi, N. Zouari (FunctionalExploration Department, H. Bourguiba Hospi-tal, Sfax, Tunisia).

We evaluated the effects of fasting duringRamadan on Insulin Sensitivity (SI) and sub-strate utilisation during exercise. Nine volun-tary women (age: 40.1 ± 2.3 years; BMI:26.23 ± 1.2 kg.m−2) underwent anthropomet-ric, blood fasting sampling with analysis ofInsulinemia (Ib) and Glycemia (Gb) and ametabolic exercise test. This test included 6 minexercise at 20, 30, 40 and 50% of theoreti-cal power and estimated the level of power atwhich energy derives mainly from glucose oxi-dation: “Crossover point” and the level of powerat which lipid oxidation is maximal “Lipox-max”. All these measures were done duringthe week before and after Ramadan. Severalindexes of SI were calculated: QuantitativeInsulin Sensitivity Check Index (QUICKI) =1/[Log (Ib) + Log (Gb)]; Homeostasis ModelAssessment for Insulin Resistance (HOMA-IR) = (Ib×Gb)/22,5; Fasting Insulin ResistanceIndex (FIRI) = (Gb×Ib)/25; the index SI =40/Ib; Ib×Gb; Ib/Gb et Gb/Ib. Fasting at Ra-madan induces a significant body weight loss(67.3 ± 2.9 vs. 66.2 ± 2.7 kg, P < 0.05) with

reduction of lean mass (43.9 ± 1 vs. 42.7 ±1.1 kg, P < 0.01) and hydrous mass (32.1 ±0.7 vs. 31.2 ± 0.7 kg, P < 0.001). “Crossoverpoint” and “Lipoxmax” were not altered afterone month fasting during Ramadan with respec-tively 47.1 ± 4.1 vs. 51.2 ± 2.4 watts (P = 0.7)and 42.4 ± 5.5 vs. 43 ± 3.3 watts (P = 0.3).Insulin sensitivity estimated by simple indexesbased on Ib and Gb was not affected by onemonth fasting during Ramadan. In conclusion,fasting at Ramadan induces a body weight losswithout any change on SI or substrate oxidationduring exercise.

Variations of the expression of serum Hsp70and the plasmatic rate of free tryptophanduring endurance exercise. A. Amara, I.Mrizak, I. Latiri, Z. Tabka, A. Zbidi (Lab-oratory of Physiology and Functional Explo-rations, Faculty of Medicine of Sousse, Av. MedEl Karoui, 4000 Sousse, BP 126, Tunisia).

Following physical exercise, several metabolicvariations take place on the level of the or-ganism. The objective of this work was to fol-low the tolerance of the sportsman to enduranceexercise according to the expression of serumHsp70 and the variation of the rate of freetryptophan. We evaluated a group of sports-men comprising 9 involved subjects of aver-age ages (19.6 ± 0.84 years), sizes (180.5 ±4.6 cm), weight (75.8 ± 9.04 kg) and VMA(16.5 ± 1.4 km.h−1). The experimental proto-col consisted in running to 65% aerobic max-imum speed during one hour. This test wascarried out on a treadmill. Two blood sampleswere taken before and with the stop of the exer-cise to analyse the expression of serum Hsp70and the plasmatic rate of free tryptophan. Ourresults show a nonsignificant increase (11.56vs. 12.68 ng.mL−1) in the expression of Hsp70and a light nonsignificant increase in the rateof tryptophan before and after the effort (2.43vs. 2.68 µmol.L−1). We note that the exercisewas responsible for the release of disturbanceswhich caused the variation of the expression ofHsp70 in various parts of the organism. Thesedisturbances reveal the installation of tirednessconfirmed by the increase in the rate of freetryptophan.

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Maximal respiratory gas exchange data inyoung Tunisian athletes: factors of variationand available norms.A. Baklouti, I. Latiri, Z.Tabka, A. Zbidi (Laboratoire de Physiologieet des Explorations Fonctionnelles, Faculté deMédecine de Sousse, Tunisia).

Aerobic physical fitness exploration, in youngathletes in the laboratory, is realised during in-cremental exercise. Representative norms of thepopulation studied are required for maximalrespiratory parameter interpretation. In fact,physical fitness assessment, in young athletes,allows the sports federation to elaborate levelgroups of training, adaptation programs and toauthorize demanders of outclassement. The pur-pose of this study was to determine specificpredictive equations of maximal respiratory gasexchange data in relation with anthropometryparameters (age (A), height (H) and weight(W)) in Tunisian young athletes. Seventy-twoyoung athletic boys aged from 9 to 16 yearsparticipated in this study. Their height andweight were respectively 155 ± 2 cm and 45 ±5.6 kg. The subjects performed an incrementalmaximum exercise test on a bicycle ergometer(Lode, Groningen) with stepwise triangular in-creasing loads at 60 rotations per minute. Anal-ysis of instantaneous gas exchange was carriedout by a breath-by-breath CPX-D/CPX CardiO2

analysis system (Medical Graphics). Anaerobicthreshold (SV1) was determined by the venti-latory equivalent method. Predictive equationswere estimated to use techniques of linear, mul-tiple regressions and the concept of allometricscaling. For statistical analysis, STATISTICAwas used. A p-value of less than 0.05 was con-sidered significant. The results show that max-imal oxygen consumption, maximal ventilationand anaerobic threshold increased significantly(P < 0.05) with anthropometry parameters. Thecorrelation analyses indicate that maximum res-piratory characteristics had the strongest cor-relation with anthropometry parameters (P <0.05). In fact, representative norm utilisation ofVO2max, VEmax and SV1 is an indispensable steptaken to propose an incremental protocol exer-cise standardisation.

BDNF participates in the anorexigenic sig-nalling in the dorsal vagal complex. B.

Bariohay, B. Lebrun, E. Moyse, A. Jean (Lab-oratoire de Physiologie Neurovégétative, Uni-versité Paul Cézanne Aix-Marseille III-UMR6153 CNRS–1147 Inra, avenue EscadrilleNormandie-Niemen, 13397 Marseille, France).

Brain-derived Neurotrophic Factor (BDNF) hasbeen implicated in the central control of food in-take, acting as an anorexigenic factor. WhereasBDNF and its receptor TrkB are expressed inthe hypothalamus and in the dorsal vagal com-plex (DVC), the two main centres involved infood intake control, previous works have beenfocused on the hypothalamus as a probable siteof action for this neurotrophin. In the ventro-medial hypothalamus (VMH), BDNF expres-sion is regulated by the nutritional state andis a downstream effector of melanocortin sig-nalling. In this study, we addressed whether, inadult rats, the DVC can be considered as a sec-ond site of action for the BDNF anorexigeniceffects. For this, we measured: (i) the effect ofintraparenchymal infusion of exogenous BDNF(provided by Regeneron) within the DVC onfood intake and body weight; and (ii) the en-dogenous BDNF protein content in the DVCand the hypothalamus, after food deprivation orperipheral treatments by the anorexigenic hor-mones leptin (provided by Amgen) and chole-cystokinin (CCK). BDNF infusion within theDVC induced anorexia and weight loss. More-over, in the DVC, BDNF protein content wasdown-regulated after food deprivation and up-regulated by leptin. CCK induced a transientup-regulation of BDNF protein content, firstin the DVC and later in the hypothalamus.These results constitute the first demonstrationthat BDNF exerts an anorexigenic effect in theDVC. Since CCK was recently shown to stim-ulate melanocortin signalling within the DVC,a tempting hypothesis is that in this structure,as in the VMH, BDNF could be a downstreameffector of melanocortin signalling.

Imaging of regional lung ventilation in miceusing Xe-enhanced quantitative synchrotronradiation computed tomography (SRCT). S.Bayat, S. Monfraix, L. Porra, C. Nemoz, G.Berruyer, W. Thomlinson, P. Suortti, A.R.A.Sovijärvi (European Synchrotron Radiation Fa-cility, BP 220, 38043 Grenoble, France).

318 Abstracts

We recently introduced a respiration gated Xe-enhanced SRCT technique that combines ex-cellent spatial resolution with the ability toboth visualize and directly quantify inhaledstable Xe gas used as a tracer, by K-edgesubtraction (KES) imaging (Bayat S, Le DucG, Porra L et al., Phys. Med. Biol. 2001,46: 3287–3299). Since KES uses x-ray beamswith narrow energy bands, sufficient flux isavailable only with high-intensity synchrotronsources. In the present study, the experimen-tal setup was miniaturized, and imaging spa-tial resolution was improved using a low-noisefast-readout (FRELON) CCD camera (pixelsize = 49 µm). Experiments were performedin 1 anaesthetized and mechanically ventilatedC57BL/6j mouse. A detailed description of theKES method can be found elsewhere (Bayat, LeDuc, Porra et al., Phys. Med. Biol. 2001, 46:3287–3299). Measurements of regional ven-tilation were based on kinetics of Xe wash-in. Single high-resolution Xe-KES tomogramswere acquired using the FRELON camera. Amap of regional specific ventilation (min−1) wasobtained, based on single compartment modelcurve fitting, and determination of Xe wash-in time constants. This technique allows func-tional lung imaging in small animals with quan-titative lung ventilation measurements. Furtherstudy will allow application in small animalmodels of obstructive lung diseases.

Study of fenugreek- seed- extracts on choles-terol and triglyceride levels in cholesterol fedrats. O. Belguith Hadriche, K. Jamoussi,A. Feki, F. Makni Ayadi (Laboratoired’Écophysiologie Animale, Faculté desSciences de Sfax, BP 802, 3018, Tunisia).

Fenugreek (Trigonella foenum graecum) isknown for its pharmacologic and nutritionalproperties. In previous studies, fenugreek-seedelicited a reduction in plasma of lipid levels.The aim of this study was to investigate theeffects of fenugreek extracts in cholesterol fedrats. Rats were divided into 8 groups as fol-lows: control, cholesterol fed group, choles-terol plus fenugreek fed group and 5 groups fedcholesterol with different extracts of fenugreek(1/ethyl acetate, 2/dichloro-methane, 3/hexane,

4/methanol and 5/water). Blood samples wereobtained to analyse cholesterol levels (CT)and triglycerides (TG). Plasma concentrationof cholesterol was increased in the cholesterolfed group and in the groups fed cholesterolwith dichloro-methane extract, hexane extract,methanol extract and water extract. However,a decrease in CT and TG was found in thosetreated with cholesterol plus fenugreek andcholesterol plus the ethyl acetate extract fromfenugreek. These results suggest that ethyl ac-etate extract from fenugreek seed opposed tothe hypercholesterolemic effect of a cholesterolenriched diet.

Beneficial effect of IGL-1, a modified UW so-lution, on a liver graft after prolonged coldischemia. I. Ben Mosbah, H. Ben Abdennebi,D. Saidane, K. Ben Mosbah, J. Roselló-Catafau, C. Peralta (Department of Experimen-tal Pathology, Institute of Biomedical Investiga-tions CSIC-IDIBAPS, Barcelona, Spain).

The hypothermic storage of livers remainsthe major approach to human liver preserva-tion because low temperature decreases themetabolism of preserved organs. The Univer-sity of Wisconsin (UW) cold storage solutionhas been introduced to decrease ischemic graftdamages. Several studies have demonstratedthat it is possible to improve cold-preservationsolutions modifying the UW solution composi-tion: the simple inversion of K+ and Na+ con-centration and the substitution of hydroxyethylstarch, one of the UW solution components, bypolyethylene glycol (PEG) in UW (IGL-1 so-lution) improves rat liver and kidney function.The present study was performed to assess theeffect of the new preservation solution: IGL-1,manufactured by the Institute Georges Lopez(Lyon, France) and a standard UW solutionon liver damage after prolonged cold ischemia(24 h). In order to evaluate the effectivenessof IGL-1 cold storage solution in liver injury,AST and ALT were measured. To appraise theseverity of liver injury after 24 h of cold is-chemia, hematoxylin and eosin-stained sectionswere evaluated by a point- counting method onan ordinal scale. The results showed that the useof the IGL–1 preservation solution significantly

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reduced hepatic damages, evidenced by de-creased AST and ALT levels in the flash efflu-ent at the end of the preservation period. Liverhistological findings after cold storage revealeda disintegration of hepatic cords when the UWsolution was used; on the contrary, with theIGL-1 solution the integrity of the hepatic cordswas maintained. This study demonstrates thesuperiority of the IGL-1 solution to protect livergrafts against prolonged ischemia damage; thismight be of interest in improving hepatic graftviability in liver transplantation.

Trimetazidine protects the rat liver againstcold ischemia injury. I. Ben Mosbah, D.Saidane, H. Ben Abdennebi, J. Roselló-Catafau,C. Peralta (Departamento de Patología Exper-imental, Instituto de Investigaciones Biomédi-cas de Barcelona (IIBB-CSIC), Rosselló 161,08036 Barcelona, Spain).

Liver transplantation has become a well-established procedure for therapy of fatal liverdiseases. In spite of dramatic improvements inthis procedure and its outcome, preservation in-jury, occurring during cold ischemia and sub-sequent reperfusion, is still considered to be acrucial factor for graft outcome in organ trans-plantation. In this context, preservation solu-tions are one of the master keys to improve theorgan quality after the preservation period. Thepresent study was performed to assess the effectof trimetazidine (TMZ, 10−6 M), an antioxidantagent, added to a UW solution on liver damageafter prolonged cold ischemia. Livers preservedfor 24 h in UW solution with and without TMZwere then flushed with 50 mL of Ringer lactate.Aliquots of the effluent flush were sampled forAST and ALT measurements, the effect of TMZon ATP level after cold storage was also eval-uated. Hematoxylin and eosin-stained sectionswere evaluated by a point- counting method onan ordinal scale. The results showed that TMZin UW significantly reduced hepatic damage,evidenced by decreased AST and ALT levelsin the effluent. Higher ATP was observed whenTMZ was added to the UW solution. Liver his-tological findings revealed a disintegration ofhepatic cords when the UW solution was used;on the contrary, by TMZ addition, the integrity

of hepatic cords was maintained. These find-ings suggest that TMZ addition in UW solu-tion could be a relevant new strategy to protectagainst cold ischemia damages that might be ofinterest in improving hepatic graft viability inliver transplantation.

Hepatotoxicity of hexachlorobenzene (HCB)in Meriones shawi shawi (Gerbillidae). S.Ben Romdane, A. Sellami (Laboratoire dePhysiologie Animale, Faculté Sciences Tunis,Campus Universitaire, 2092 El Manar, Tunis,Tunisia).

HCB is an organochlorinated pesticide whichbelongs to the family of persistent organic pol-lutants (POP). Used for a longtime as a fungi-cide in agriculture, its utilization was stopped in1972. However, it continues to be produced asan unintentional by-product in the manufactur-ing of chlorinated solvents. With its resistanceto environmental degradation and its mobility,HCB is widely distributed throughout the worldand even in Tunisia. Many epidemiologic stud-ies have shown the dangerous effects of HCBon living creatures. The aim of this work was toevaluate the effects of a subacute exposition ofHCB on the body weight and liver of a desertrodent, Meriones shawi shawi. Females Meri-ones were submitted to gavage with the dosesof 0 mg (control group), 0.16 mg, 4 mg and16 mg.kg−1 b.w./day during 30 days. Our resultsshow a significant decrease of the body growthin the three treated groups. The liver weight wasnot affected with 0.16 and 4 mg.kg−1 b.w./day ofHCB; a significant increase was observed withthe highest dose (16 mg). The hepatic glyco-gen stores were reduced with the treatment inall treated groups. The histological structureof the liver was altered by HCB showing vac-uolization of the cytoplasm being more impor-tant with the dose of 16mg. These results reveala hepatotoxicity of these low doses of HCB inthis species.

Maximal anaerobic power is not altered byprior exercise with a different muscle group.E. Bouhlel, S. Chelly, I. Mrizak, Z. Tabka(Unité de Recherche, Institut Supérieur duSport et de l’Éducation Physique, Kef, Tunisie).

320 Abstracts

The aim of this study was to examine whetherblood lactate production at the end of a force-velocity test with legs contributed to a reduc-tion of the maximal anaerobic power (Wmax)performed with arms. Seven well-trained sub-jects (age: 20 ± 2, height: 181 ± 7 cm, weight:86 ± 14 kg) performed two protocols that con-sisted of two consecutive force-velocity testswith legs and then with arms: (i) Arm crank-ing force-velocity test (A1) followed by legcycling force-velocity test (L2). Eight minutesrest separated A1 and L2. (ii) Leg cyclingforce-velocity test (L1) followed by arm crank-ing force-velocity test (A2) on a Monark cy-cle ergometer (type 894 E). Eight minutes restseparated L1 and A2. Blood lactate value atrest averaged 1.6 ± 0.3 mmol.L−1. Blood lac-tate concentrations after A1 and L2 were 6.8 ±1.4 and 6.2 ± 1.8 mmol.L−1 respectively. Bloodlactate after L1 and A2 were 5.7 ± 1.3 and6.5 ± 1.5 mmol.L−1 respectively. The priorforce-velocity test with legs did not alter thefollowing maximal anaerobic power performedwith arms and vice versa: Wmax-A1 and Wmax-A2 were 594 ± 126 W and 581 W ± 145 re-spectively (NS); Wmax-L1 and Wmax-L2 were1041 ± 283 W (12 ± 2.6 W.kg−1) and 1081 ±353 W (12.6 ± 3.2 W.kg−1) (NS). In conclu-sion, the repetition of 6 to 8 sprints during aforce-velocity test (Vandewalle, 1986) with legsinvolve blood lactate production. However, thisproduction does not alter the Wmax performedwith arms. Maximal anaerobic power is not al-tered by prior exercise with a different mus-cle group. The force-velocity test with legs andwith arms could be used consecutively in thelaboratory to evaluate the Wmax in trained ath-letes.

Expression of extracellular matrix compo-nents and their integrin receptors in theadult rat adrenal gland. S. Campbell, M.Otis, N. Gallo-Payet, M.D. Payet (Départe-ment de Physiologie et Biophysique, Facultéde Médecine et des Sciences de la Santé, Uni-versité de Sherbrooke, 3001, 12e avenue, Sher-brooke, Québec, Canada).

The binding of integrins to extracellular matrix(ECM) components triggers intracellular path-ways that are involved in adhesion, migration,

proliferation and cell survival. We used im-munohistochemistry and indirect immunofluo-rescence techniques to investigate the presenceof ECM components and integrins in the adultrat adrenal glands. We showed that collagentype I was expressed in the adrenal capsule,was found as short fibrils in the adrenal cortexand was present around adrenal medulla cells.Collagen type IV staining was found in thezona glomerulosa and as long fibrils throughoutthe cortex with a weak labeling in the capsule.Laminin and fibronectin were both expressedin the capsule and in the zona glomerulosawith fibrils entering the inner zones of the cor-tex. Like collagen I, collagen IV, fibronectinand laminin staining was also observed aroundcell clusters of the medulla labeled with anti-dopamine beta hydroxylase antibody. Integrinsubunits α1 showed a strong labeling in theadrenal medulla with a weak staining in the cor-tex. The α2, α3 and α5 showed strong stain-ing in the adrenal cortex with some cells la-beled in the medulla. Integrin subunits α8 andβ1 were detected throughout the adrenal glandwith no specific expression pattern. Localiza-tion of ECM components and their associatedintegrins provide important information to un-derstand specific function related to each zoneof the adrenal cortex, like proliferation and al-dosterone secretion in the zona glomerulosa ormigration and secretion of corticosterone in thezona fasciculata.Funded by Canadian Heart Foundation to NGP andMDP.

Ubiquitin/proteasome pathway as an earlyprotective mechanism against hyperoxia inthe airway. A. Chambellan, S.A. Comhair,K.A. Szabo, P. Cruickshank, P. MacKenzie,S.C. Erzurum (Institut du Thorax, CHU Nantes,44093 Nantes Cedex 1, France).

Human bronchial epithelial cells are vulnera-ble to hyperoxia and fail to increase the pri-mary intracellular antioxidant enzymes suchas superoxide dismutases, catalase or glu-tathione peroxidases. Because of this inabil-ity to enhance an appropriate antioxidant re-sponse against hyperoxia and the accumulationof oxidatively modified proteins in bronchial

Physiology Society Symposium 321

epithelial cells, we postulate that other pro-tective mechanisms involved in protein degra-dation, e.g. the ubiquitin-proteasome pathway,may have a central role at the early phase tomaintain the homeostasis of the epithelial layer.In order to evaluate the first events to the adap-tive response to hyperoxia, we examined geneexpression of bronchial epithelial cells by usinga large scale microarray approach. We analysedthe mRNA levels of human bronchial epithe-lial cells in 8 healthy volunteers obtained frombrushing at bronchoscopy before and after 12–16 h exposure to > 95% O2. We describe thegenes modulated by hyperoxia gaining insightsinto the underlying biological altered functions.The processes involved confirmed the ubiqui-tin dependent protein catabolism pathway tobe the main early response to hyperoxia. Be-cause of the few numbers of subjects enrolledin the study and the individual polymorphismin gene expression causing variability, we con-firmed our results by using human bronchial ep-ithelial cells (BET-1A) exposed to > 95% O2 inan in vitro study. Our findings indicate that pro-tein processing and catabolic pathways, whichare critical for preventing accumulation of oxi-dised and/or misfolded proteins in the cells, areinvolved in the early response of the airway ep-ithelium to oxidative stress.

Low-voltage electrical stimulation improvesblood flow and enhances angiogenesis in is-chemic rat skeletal muscle. P. Dobšák, M.Nagasaka, J. Siegelová, J. Jancík, J.-C. Eicher,JE. Wolf, K. Imachi, M. Kohzuki (Departmentof Functional Diagnostics and Rehabilitation,St. Anna Faculty Hospital Brno, Faculty ofMedicine, Masaryk University, Pekarská 53,656 91 Brno, Czech Republic).

Electrical stimulation of the skeletal muscle hasbeen reported to promote vascular endothelialgrowth factor (VEGF) production but inductionof angiogenesis in the muscle by low-voltageelectrical stimulation (LVES) is not fully un-derstood. This study was designed to assessthe effects of LVES on blood flow restora-tion in ischemic skeletal muscles, and to in-vestigate whether LVES-induced VEGF is dueto the hypoxia or inflammation by measuring

hypoxia-inducible factor (HIF-1α) and inter-leukin (IL-6). In-vivo experiments of hind limbischemia (with bilateral excision of femoralarteries) were conducted on male Sprague-Dawley rats (n = 7). A stimulating electrodewas implanted into the right tibialis anteriormuscle (RTAM); the left one (LTAM) servedas a control. Continuous LVES was maintainedfor 5 days (frequency 25 Hz; voltage 0.1 V;24 h/day). Then, the evaluation of blood sup-ply in RTAM and LTAM was done using laser-Doppler imagery (the results are expressedin relative units – RU); VEGF concentra-tions from muscle samples were determinedby the ELISA assay, and the levels of HIF-1α and IL-6 by immunohistochemical stain-ing. Five days of LVES significantly increasedblood supply in RTAM (489.3 ± 61.5 RUvs. LTAM 348.7 ± 32.6 RU; P < 0.0277),and also the VEGF production in stimulatedRTAM (131.7 ± 9.6 ng.L−1 vs. LTAM 110.3 ±9.6 ng.L−1; P < 0.01). No significant differ-ences were observed in tissue levels of HIF-1α and IL-6 in stimulated or non-stimulatedTAM. In conclusion, continuous LVES in skele-tal muscles could be effective in angiogenesisenhancement and blood supply restoration, andcould have an important therapeutic value in is-chemic vascular diseases.

Study was supported by grants: IGA MZ CR NR-7893-3, MSM 0021622402 and TUBERO (Sendai).

Rugby practice and skeleton: correlationsbetween strength, BMD and biochemicalmarkers of bone remodeling. M. Elloumi,D. Courteix, S. Sellami, Z. Tabka, G. Lac(LPPM, Université Clermont II, 63177 Aubiere,France).

This study reports observed correlations be-tween muscular strength, bone mineral den-sity (BMD) and content (BMC), biochemicalmarkers of accretion (osteocalcine) and resorp-tion (C-telopeptide or CTx) in rugby players.Twenty male rugby players of the Tunisianrugby team (25.6 ± 0.8 years, 178.3 ± 1.3 cm,92 ± 3.3 kg, 17.1 ± 1.3% LBM); Strengthmeasurements: handgrip + Bosco mat; BMD:double X ray absorptiometry; Biochemicalmarkers dosage: Emethods. Positive significant

322 Abstracts

correlations (P < 0.001) were shown betweenstrength and total and regional (rachis, legs,femoral neck which are specifically stressed bythis sport practice) BMD. In the same way, theosteocalcin, but not CTx, was highly correlatedwith the same regional BMD and total BMD.In a previous study, we show that rugby playerspresent higher BMD and BMC than sedentarypeople, and among rugbymen, that forwardsparticularly had higher BMD than backs, on ac-count of impact number and struggle phasesthey have to sustain (Elloumi, Courteix, Sel-lami, Tabka, Lac, Int J Sports Med 2006 (inpress)). This study was done to verify if strengthcharacteristics might be correlated to biochemi-cal markers of bone metabolism. It appears thatthe muscular strength, which is itself correlatedto the lean body mass, is a major determinant ofthe skeleton quality. Moreover, the correlationreported between the BMD and the osteogenicmarker osteocalcin, suggests that this positivebone adaptation may be linked to an improve-ment of the bone remodelling speed.

Progressive isometric strength training re-stores endothelial function in ovariectomizedfemale rats. H. Figard, V. Gaume, F. Mougin,A. Berthelot (Laboratoire de Physiologie,Faculté de Pharmacie, place Saint Jacques,25030 Besançon Cedex, France).

Exercise training enhances vasodilation viaaugmented endothelial release of nitric ox-ide (NO). Ovariectomized rats develop a typi-cal endothelial dysfunction resembling that ob-served in postmenopausal women. The aim ofthis study was to investigate whether a pro-gressive isometric strength training protectsagainst endothelial dysfunction induced by es-trogen deficiency in female rats, as efficientlyas 17β-estradiol. Twenty-four female Sprague-Dawley rats (4 weeks old) were subjected to abilateral ovariectomy (OVX). Eight sham oper-ated animals (SHAM OVX) served as the con-trol. After surgery, the animals were randomlyassigned to one of the four treatment groupsfor 14 weeks as follows: (i) a sedentary con-trol group receiving subcutaneous (s.c.) dailyinjection of 17β-estradiol 20 µg.kg−1 (OVXSED17β); (ii) sedentary control group receiv-

ing daily vehicle s.c. (OVX SED); (iii) progres-sive isometric strength training group (everymorning, 5 days/week), receiving daily vehicles.c. (OVX ISO); (iv) sedentary sham operatedgroup (SHAM OVX). Endothelium responsewas evaluated with cumulative concentrationsof acetylcholine (ACh 10−10–10−5 M) in aor-tic rings precontracted with norepinephrine(10−7 M). The concentration-response curvesfor ACh demonstrated that ACh-induced va-sodilation was enhanced in aortic rings ob-tained from the OVX ISO group, as evidencedby the highest pD2 value (7.77 ± 0.11) com-pared to OVX SED (7.17 ± 0.14) and SHAMOVX (7.24 ± 0.09) groups. 17β-estradiol treat-ment increased endothelium-mediated vasodi-lation in OVX SED17β compared to OVX SEDrats, however exercise training significantly im-proved endothelial function to a greater extentas compared to 17β-estradiol. The present re-sults show, that isometric strength training isassociated with improvement of ACh-inducedvasodilation in ovariectomized female rats. Theability of physical activity to counteract en-dothelial dysfunction suggests its potentiallyuseful role in the prevention of cardiovasculardiseases.

The results of a food consumption surveycarried out in French high level rugby play-ers. J. Finaud, M. Elloumi, F. Maso, H. Vidalin,A. Robert, G. Lac (BAPS, Biologie B, LesCézeaux, 63177 Aubière, France).

The objective of this study was to evaluatethe dietary intake in high level rugby players(n = 26, 26.9 ± 2.9 years, 185.9 ± 8.7 cm,98.9 ± 13.9 kg, 16.6 ± 2.4% MG) accord-ing to the seven-day dietary intake method andto compare the results with the allowed stan-dard values. The global caloric intake (3267 ±636 kcal.d−1) was in agreement with the RDA.At the qualitative level, the same bias as forthe sedentary populations might be noted: toolow complex carbohydrates and polyunsatu-rated free fatty acids, too many lipids, particu-larly saturated free fatty acids, monounsaturatedfree fatty acids and cholesterol. The ratio of pro-teins and micronutrients seem adequate for thispopulation even if certain subjects show deficit

Physiology Society Symposium 323

signs in magnesium, calcium, zinc, and in vita-mins D or C. Correlations were shown betweenfat-mass and global caloric intake (P < 0.001)and more particularly between the fat mass andglobal lipid (P < 0.05), saturated fatty acid(P < 0.05), and cholesterol (P < 0.001) in-takes. Since the fat mass was itself negativelycorrelated with VO2max (P < 0.001), it may bepostulated that these dietary bias impact nega-tively on physical performance. Thus, the rugbyplayers will probably draw benefits of some nu-tritional advice for their health and sport perfor-mance.

The anthropometric index, lipid metabolismand insulinoresistance index in the glucoseintolerance. A. Ghouini, K. Khelfat (Labora-toire de Physiologie, Faculté de Médecine deBlida, 9000 Blida, Algeria).

This work was aimed at appreciating the obe-sity incidence (by means of body mass index“BMI” and waist/hip ratio “WHR”), by fast-ing blood lipoproteins, glucose and insulin dur-ing the glucose intolerance. Blood lipoproteins,glucose and insulin dosage, as well as the calcu-lation of the glucose/insulin “G/I” relationship(insulin resistance index) were effected in nor-mal, glucose intolerant obese and glucose intol-erant normal weighed subjects (20 subjects ineach group). At the end of this study, it wasclear that insulin resistance is shared in an al-most equal way in glucose intolerant obese sub-jects and in normal weighing ones. The twofactors which are charged in insulin resistance(BMI and WHR) did not show in our study anyrelationship with insulin resistance in glucoseintolerants classified according to their “BMI”or “WHR”. However, the VLDL and LDL con-centrations were elevated in obese subjects. Itis possible that lipid metabolism and insulin re-sistance index are not associated perhaps formany nutritional and metabolic reasons.

Altered antioxidant status in spontaneously-hypertensive rats fed a fructose-enricheddiet.A. Girard, S. Madani, F. Boukortt, J.Belleville, J. Prost (UPRES Lipides et Nu-trition, 6 boulevard Gabriel, 21000 Dijon,France).

High fructose doses mainly consumed in in-dustrial countries have been shown to inducemetabolic abnormalities such as hyperinsuline-mia, insulin resistance, dyslipidemia, clusteredas syndrome X. The changes in antioxidantdefense are unknown in hypertension associ-ated with metabolic disorders induced by ahigh fructose diet. Twenty spontaneously hy-pertensive rats (SHR) were divided into 2groups. The fructose-fed animals received afructose-enriched diet (60% fructose) whilecontrol animals received a control diet contain-ing starch (60%). After a 13-week-diet period,the total antioxidant status was performed inblood and liver by monitoring the rate of freeradical-induced RBC hemolysis (KRLTM test).Lipid peroxidation was assessed in plasma, theVLDL-LDL fraction and liver as the produc-tion of thiobarbituric acid reactive substances(TBARS). Antioxidants (enzymes and vita-mins) were determined respectively, in blood orplasma and in the liver. Compared with con-trols, rats fed the fructose diet showed similarblood pressure but hyperglycemia and plasmahyperinsulinemia. The fructose diet increasedboth plasma and VLDL-LDL TBARS concen-trations and decreased liver TBARS levels. Inthe fructose group, Cu/Zn-SOD and GSH-Pxactivities were significantly lowered in erythro-cytes whereas they were increased in the liver.The non enzymatic defense system was also af-fected in the plasma of the fructose group, byincreased ascorbic acid levels and decreased α-tocopherol and retinol concentrations. Feedinga fructose-enriched-diet negatively affects theantioxidant capacity in the blood of hyperten-sive rats, but it has no deleterious effect on theliver suggesting a better defense in this organ.

Determinants of membrane factor (Dm) andcapillary lung volume (Vc) in healthy sub-jects. S. Glénet, C. de Bisschop, R. Dridi, H.Guénard (Laboratoire de Physiologie EA 518,Université Bordeaux 2, Faculté des Sports dePoitiers, France).

The main determinants of Dm and Vc inhealthy subjects were analysed using theNO/CO method (Guénard et al., Respir Physiol1987, 70: 113–120). Twenty-five subjects 24 to

324 Abstracts

63 years old, 20 men and 5 women, were in-cluded in the study. Maximal oxygen consump-tion was measured as well as Dm and Vc witha Medisoft equipment (Dinant, Belgium). Sev-eral measurements were performed at total lungcapacity (TLC) as well as at 65 and 80% TLC.Measurements were also performed during pos-itive (+12 h Pa) or negative pressure (–9 h Pa)breathing. Vc in standard condition at TLC de-pends on lung volume, age and oxygen con-sumption Vc = (33.6 + 12) × VA – (0.9 × âge)+ (0.7 × VO2max) (r = 0.9; P < 0.05). The maindeterminant of Dm was the lung volume. Dmincreased by 58% between 65 and 100% TLC,as the increase in Vc was meaningless. Posi-tive pressure breathing decreased Vc slightly asnegative pressure breathing increased Vc signif-icantly from 115 to 126 mL. The relationshipbetween Dm and lung volume was not linear, ofthe type Dm = 24.6 × V0.8

L (r = 0.96), suggest-ing that the lung neither behaves like a bellow,in which case the relation would be linear, orlike a simple bubble in which case the exponentof the relationship would be 0.67. Dm and Vcappeared very sensitive to different physical de-terminants which could associate their effects inphysiological situations such as change in posi-tion or muscular exercise.

Chromosomal damage in turbot (Scophthal-mus maximus) exposed to fuel oil. Com-parison of two contamination protocols. C.Goanvec, T. Lacoue-Labarthe, H. Ollivier, M.Theron, K. Pichavant, E. Poirier, S. Le Floch, J.Laroche, V. Maxime, L. Nonnotte, G. Nonnotte(Unité de Physiologie Comparée et Intégrative,UFR Sciences et Techniques, 6 Av. le GorgeuCS 93837, 29238 Brest Cedex 3, France).

Turbots (Scophthalmus maximus), were ex-posed to fuel oil number 2, either intraperi-toneally (with two doses) or with contaminatedwater. Biliary metabolites were evaluated byfixed fluorescence to verify the efficiency ofintoxication. EROD activity was compared tochromosomal damage measured by flow cytom-etry. Biliary metabolite analyses showed a gooddose/response relation and constituted a clearreference for the subsequent measurements.Comparing flow cytometry and EROD results,

a shorter delay of response for EROD activ-ity was obtained. The persistence of EROD re-sponse was shorter while the genotoxic signalstill persisted after one month. The measure-ment of chromosomal damage allowed a gooddifferentiation between the two tested doses; inthe case of EROD activity, the results were lessclear. These results suggest that within a fewweeks, after exposure to fuel oil number 2, themeasurements of chromosomal damage by flowcytometry can be used to detect a dose depen-dant genotoxic response in fish.

Superoxide dismutase activity in macro-somic newborns. O. Grissa, A. Kasdallah-Grissa, M. Jebi, A.H. Miled, M. Bibi, Z.Tabka (Service de Physiologie et des Explo-rations Fonctionnelles, Hôpital UniversitaireFarhat Hached, 4000 Sousse, Tunisia).

Low birth weight has appropriately been thefocus of extensive health policy and researchendeavours, but high birth weight, also asso-ciated with adverse maternal and infant out-come, has received less focus inquiry. The pur-pose of this preliminary study was to evaluatethe oxidative stress in macrosomic newbornsand their mothers. Superoxide dismutase lev-els as an indicator of oxygen radical activitywere determined in both maternal and umbilicalcord blood. The comparison was made betweenmacrosomic newborns (n = 20) with meanweight 4330 ± 0.05 g, size 48.65 ± 0.43 cm andcranial perimeter 34.05 ± 0.23 cm and normo-somic newborns (n = 20) who weighed 3120 ±0.10 g, and have 49.33 ± 2.34 cm of size and35.58 ± 0.29 cm of cranial perimeter. The samecomparison was made between their moth-ers. Our results showed that erythrocyte SODactivity was significantly reduced (P < 0.01)in macrosomic babies (452.21 ± 67.43 U.g−1

Hb) when compared with the control babies(1159.10 ± 114.91 U.g−1 Hb). The maternallevels of SOD showed the same result withmean values about (646.21 ± 76.69 U.g−1 Hb)in women who had macrosomic babies and(1405.00 ± 202.00 U.g−1 Hb) in the controlwomen. The percentage decreases in SOD lev-els were 70% and 54% for babies and moth-ers, respectively. We note that enzyme activity

Physiology Society Symposium 325

is significantly lower (P < 0.05) in cord bloodsamples than the maternal values in both macro-somic cases and controls. Decreased activityof the enzyme scavenger, superoxide dismu-tase, which catalyses the dismutation of O·−2into H2O2 indicates a deficiency in the antioxi-dant defence system during macrosomia and theimplication of oxidative stress. Based on thesefindings, it is speculated that foetal macrosomiais associated with alteration in antioxidant sta-tus in babies and their mothers. This parameterhas the potential to show the efficacy of usingantioxidants such as vitamin E and/or vitaminC to reduce oxidative stress in macrosomic ba-bies and the risk of foetal and maternal compli-cations.

The effects of TRH in the adult male rat.F. Hadj-Bekkouche, R. Djediat, A. Naroun(LBPO, Endocrinologie, Faculté des SciencesBiologiques, USTHB BP 32 El Alia Bab-Ezzouar, Alger, Algeria).

TRH has been isolated from the mammalian hy-pothalamus. It plays a central role in regulat-ing the pituitary thyroid axis. The purpose ofthis study was to examine the effects on thethyroid axis and the genital system. Two doseswere used, 200 µg.mL−1 and 250 µg.mL−1,and injected intraperitoneally. The duration ofthe treatment varied from four to eight days.The Wistar rats were divided into three groups:group 1 (n = 16) received 250 µg.mL−1 forfour days, group 2 (n = 8) 200 µg.mL−1 foreight days and group 3 (n = 15) 250 µg.mL−1

for eight days. Two control groups were con-sidered in each group, one (C, n = 5) withoutinjection and the other (T, n = 5) received thesame volume of the vehicle (NaCl%�). All theanimals were weighted daily. The body weightincreased significantly (P < 0.001) with TRH200 µg.mL−1 and 250 µg.mL−1 (P < 0.05) foreight days. FT3 increased significantly (P <0.02) compared to control C and reduced sig-nificantly (P < 0.02) compared to controlT. Plasma testosterone concentration showed asignificant decrease (P < 0.05). The follicularepithelium of the thyroid was significantly (P <0.001) reduced. The average height of the epi-didyme appears to be significantly (P < 0.001)

lower than the control 1 and 2. The results indi-cate that TRH increases body weight. This ef-fect may be due in part to GH. Moreover, it re-duces plasma testosterone and this is probablyinvolved in the decrease of the epithelium of theepididyme. On the thyroid axis, TRH might re-duce the effects of stress.

Low calorie-diet and ageing. K. Hamdena, A.Elfeka, S. Carreaub (a Écophysiologie Animale,Faculté de Sciences, Sfax, Tunisia; b Biochimie,USC Inra, Université, Caen, France).

The time effect on living organisms shall beconsidered at various stages from the molecu-lar level to the whole individual and the soci-ety. Following the free radical theory [Harman,1956], numerous works have been publisheddealing with the deleterious effect of oxygenand oxidative processes on molecular ageingespecially on the cell membrane. The aim ofthis work was to analyse the putative relation-ship between diet energy and ageing. Male Wis-tar rats aged of 5 months were bred under thesame conditions with free access to a pelletdiet. Three groups (n = 8 per group) of an-imals were studied: a control group (C) witha diet of 335 kcal.day−1.kg−1 body weight, agroup (R1) receiving 248 kcal and a third groupwith the lower calorie-diet (R2) of 165 kcal.These treatments were performed during 6, 7,9, 10 and 12 months. Among the different pa-rameters measured during the study, only datarelated to malonedialdehyde (MDA) are pre-sented. Indeed, it is well known that MDAis a good marker of cell membrane damagefollowing ROS production during stress. Inthe control group, MDA levels increased by50% in the liver between 6 and 12 months(12–24 nmol.g−1, respectively), 44% in thespleen (24–42 nmol.g−1), 20% in the kidneys(40–50 nmol.g−1) and 29% in the testes (11–15 nmol.g−1). In the group R1, the MDA lev-els increased but much lesser than in the con-trol group (–20% for the liver; –11% in thespleen; 63.6% in the kidneys and –20% in thetestes compared to MDA in untreated animals).In the animals fed with the lowest energy diet,the MDA levels were similar to those of thecontrol group. Consequently, we may conclude

326 Abstracts

that a low calorie diet (R1) without changing thequality of the pellet and which does not induce astarving behavior (R2) is likely suitable to pro-tect against (lower MDA level) or delay the ap-parition of cell membrane damage consecutiveto ageing in the male rat.

Effects of atherogenic diets in Psammomysobesus. N. Hamlat, S. Neggazi, Y. Benazzoug,G. Kacimi, S. Chaïb, S. Aouichat-Bouguerra(Nutrition and Metabolism laboratory, FSB,USTHB, PO Box 32, 16111 El Alia, Algiers,Algeria).

Since vascular complications often accompanydiabetes, Psammomys obesus is a model ofhuman nutritionally induced diabetes whentransferred from its native halophilic plantnutrient to the standard laboratory diet, inap-propriate to their metabolic capacity. In or-der to compare the effects of two athero-genic diets and the nutritional interaction,three groups of Psammomys were exposedto a six month protocol: a natural diet (20–22 cal.day−1); natural diet and 1/4 egg yolk(40 cal.day−1); standard laboratory diet and 1/4egg yolk (52.5 cal.day−1). Hyperglycemia andhypertriglyceridemia were more pronouncedin animals maintained on halophilic plantand egg yolk than in Psammomys main-tained on a standard diet and egg yolk; amarked hypercholesterolemia characterised thetwo groups receiving egg yolk (superior to1500 mg.dL−1). Hyperproteinemia appeared atthe second month of experimentation and wasmore pronounced in Psammomys on a natureldiet with egg yolk. A high level of productionof atherogenic lipoproteins (VLDL-LDL) anda decrease of antiatherogenic fractions (HDL)were registered in the two groups of experimen-tal Psammomys. At autopsy, the hepatic con-tent indicates that the increase of total lipidin Psammomys on a halophilic plant diet withegg yolk is more important (296%) than inPsammomys on a standard laboratory diet withegg yolk (110%); the reason for each histologyshowed that the hepatic steatosis was more pro-nounced in the first group. The histological ex-amination of the thoracic aorta showed impor-tant alteration in two groups of Psammomys on

an atherogenic diet (blood aggregation, prolif-eration and migration of smooth muscle cells,collagen accumulation and elastolysis) but thedramatic effects were only revealed after the ad-ministration of halophilic plant with egg yolk (acut of the aortic segment).

Interactions of caloric restriction with cy-totoxic effects of nickel chloride in stressprotein expression in rats. N. Hfaiedh, M.S.Allagu, F. Croute, J.P. Soleilhavoup, A. El Ffeki(Laboratoire Écophysiologie Animale, Facultédes Sciences de Sfax, BP 802, 3018, Tunisia).

Nickel and Ni compounds are well recognisedcarcinogens. Indeed, increased risks of lungand nasal cancers have been detected in peo-ple working in Ni industries. It is suggestedthat the NiCl2 induced toxicity might be me-diated by generation of H2O2 and/or by in-duction of the Fenton reaction which generateshydroxyl radicals. Recently, low amounts of re-active oxygen species (ROS) were detected inA549 cells exposed to NiCl2 (250–1000 µM)for 45 min (Salnikow et al., 2000). An overexpression of specific stress proteins such asheat shock proteins (HSP) was shown to fol-low the accumulation of misfolded proteins incells. HSP are known to act as molecular chap-erones to restore the correct folding of damagedproteins. They are also crucial in reinstallingcellular homeostasis. The present study dealswith the effects of Ni on the expression levelof the cytosolic HSP72/73 and the reticulum-associated GRP94. Experiments were carriedout on Wistar female rats (3 months old, 130 gbody weight) who were randomly divided intotwo batches: the normally fed (N) batch wasgiven 20 g of food pellets per animal daily. Theanimals submitted to diet restriction (J) weregiven the same amount of food pellets 1 dayover two. After one month, each batch was di-vided into two groups. The animals were in-jected daily, for 10 days, with either 4 mg.kg−1

body weight NiCl2 or with the same volumeof saline solution. Another set of experimentswere carried out using cell lines derived fromthe human lung (A549). The cells were culturedfor 4 days in the permanent presence of 100,200, or 400 µM NiCl2. The Ni induced over

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expression of HSP73 and GRP94 in the kidneysof rats and in A549 lung cells. In this respect,the important lowering of the HSP72 we ob-served under our experimental conditions in thekidneys of rats and in the cell lines is puzzlingand the mechanism underlying this effect is stillspeculative. No such effect was observed in thekidneys of rats submitted to intermittent fastingin stress proteins. This could be related to thefact that nickel was shown to generate reactiveoxygen species and caloric restriction was asso-ciated with a decrease of free radical generation.

Improvement of regional blood supply byelectrical stimulation of strength musclesin patients with end-stage congestive heartfailure. J. Jancík, P. Dobšák, J. Siegelová,H. Svacinová, J. Vítovec, P. Balcárková, L.Kožantová, J.C. Eicher, J.E. Wolf (Departmentof Functional Diagnostics and Rehabilitation,St. Anna Faculty Hospital Brno, Faculty ofMedicine, Masaryk University, Pekarská 53,656 91 Brno, Czech Republic).

This study was designed to investigate theinfluence of low-frequency electrical stimula-tion [LFS] of strength muscles on regionalblood flow in patients with advanced formof congestive heart failure [CHF]. Fifteen pa-tients with CHF [mean age 51.5 ± 7.2 years,class NYHA III-IV, mean EF 19.8 ± 3.5%]underwent 6-week stimulation training usingLFS (frequency 10 Hz; amplitude 60 mA;60 min/day; 7 days.week−1) applied simultane-ously to quadriceps and calf muscles of bothlegs. Blood flow velocity (BFV) of the rightfemoral artery and cardiac output (CO) weremeasured at the baseline and at the end ofthe training period by pulsed-wave Doppler ve-locimetry and by trans-thoracic echocardiogra-phy. Systolic blood pressure (SBP), diastolicblood pressure (DBP) and heart rate (HR) weremonitored during each period of stimulation[in 15-min intervals]. Six weeks of LFS sig-nificantly increased the mean blood flow ve-locity in the right femoral artery compared tothe value at the baseline (48.2 ± 4.1 cm.s−1 vs.35.6 ± 3.9 cm.s−1; P < 0.05). There were nosignificant differences in the values of CO mea-sured at the baseline and at the end of the train-

ing period; the measurement of SBP, DBP andHR did not show any significant changes duringthe stimulation. In conclusion, long-term regu-lar application of LFS of strength muscles couldimprove the blood supply in stimulated mus-cles in patients with CHF. The results presentedalso demonstrate that LFS is a safe and well-tolerated method, without life-threatening sideeffects.Supported by grants: IGA MZ CR NR-7893-3, MSM0021622402 and TUBERO (Sendai).

Physical activity and obesity in Down syn-drome. S. Joffroy, S. Geneau, A. Durieu,S. Garnier, S. Lemoine, P. Mauriège (UFR-STAPS, Université de Toulouse III, 118 Routede Narbonne, 31062 Toulouse Cedex, France).

The prevalence of overweight and obesity inDown syndrome was investigated in 578 chil-dren and adults living in different communi-ties in France. Body Mass Index (BMI) andits relations with selected anthropometric mea-sures, environmental factors as dietary habitsand physical activity were determined. Males(45.4%) and 61% females were categorised asoverweight and obese according to the classifi-cation of OMS (1998). The middle BMI in ourpopulation was more important than that ob-served in the French population (25.4 kg.m−2

vs. 24.4 kg.m−2), and was always higher inwomen than in men, irrespective of age (26.9 ±6.7 kg.m−2 for females vs. 24.5 ± 4.9 kg.m−2 formales, P < 0.05). The middle BMI increasedwith age from 41–50 years and decreased after60 years. Physical activity alone had a great in-fluence on BMI, irrespective of the volume andtype of activity (endurance, or not). Even if thecause of obesity in people with Down syndromeis unknown but is probably multifactorial, itmay involve poor eating behavior, calorie in-take, depressed metabolic rate, reduced exer-cise, hypotonia and endocrine abnormalities. Inconclusion, our results show physical activityinduces an important reduction of BMI in theDown syndrome population. Other investiga-tions should be considered when studying thecourse of this pathology.

Respiratory muscle oxygenation kinetics:relationships with breathing pattern. R.

328 Abstracts

Legrand, F. Prieur, A. Marles, C. Nourry, N.Blondel, S. Lazzari, P. Mucci (Laboratoired’Analyse Multidisciplinaire des PratiquesSportives, UFR Staps, chemin du Marquage,62800, Liévin, France).

We purpose to investigate respiratory muscleoxygenation kinetics monitored by NIRS andto study relationships with breathing parame-ters, in young healthy subjects, during exercise.Nineteen young males performed a maximal in-cremental test on a cycle ergometer to deter-mine maximal oxygen consumption (VO2max),and to locate changes in the breathing patternby studying the VO2 corresponding to an ac-celerated rise in breathing frequency (Fbacc),plateau of tidal volume (Vtplateau) and inflectionpoint in the VE/Vt relationship (VE/Vtinflection).First and second ventilatory threshold (VT1 andVT2) were also determined. Respiratory mus-cle deoxygenation (RMD) kinetics were mon-itored by NIRS. VO2 at which RMD was ac-celerated (RMDacc) and the amplitude of RMDat maximal exercise (∆OXY) were determined.All subjects showed significant RMD. VO2 cor-responding to RMDacc and to change in breath-ing pattern were not different. Relationshipswere found between the VO2 corresponding toRMDacc and the VO2 corresponding to Fbacc

(r = 0.88, P < 0.001), Vtplateau (r = 0.84,P < 0.001), VE /Vtinflection (r = 0.58, P < 0.05)or VT2 (r = 0.79, P < 0.001). ∆OXY was re-lated to VO2max (r = 0.58, P < 0.05). In con-clusion, RMDacc seems to be due to the changein breathing pattern and especially to the im-portant rise in breathing frequency at this inten-sity level, i.e. VT2. Moreover, subjects who ex-hibit higher VO2max also exhibit higher RMD.This supports the hypotheses that (i) respiratorymuscle oxygenation participates significantly intotal VO2 during strenuous exercise (ii) the res-piratory muscle share of whole body VO2 be-comes more elevated as the level of aerobic fit-ness increases.

Outlow tract obstruction during exercise inhypertrophic cardiomyopathy impaired pri-mary hemostasis. T. Le Tourneau, S. Susen, A.Millaire, A.S. Polge, C. Caron, N. Lamblin, P.de Groote, G. Deklunder, C. Bauters, B. Jude

(Inserm ERI-9, EA 2693, University of Lille,Service d’EFCV, Hôpital Cardiologique, Bd PrJ. Leclercq, 59037 Lille Cedex, France).

Outflow gradient in hypertrophic cardiomyopa-thy (HCM) might impair primary hemosta-sis with Willebrand factor (VWF) proteoly-sis. The magnitude of the outflow gradientmay vary with numerous physiological alter-ations. In HCM, we sought to evaluate (i)the relationships between outflow gradient andVWF impairment, and (ii) the effect of ex-ercise on gradient and VWF. Thirty-five pa-tients (44 ± 16 y) with either obstructive(HOCM, 6) or non obstructive (HCM, 29) hy-pertrophic cardiomyopathy underwent a semi-supine symptom-limited exercise echocardio-graphy (EE). Selected parameters reflectingVWF abnormalities were evaluated under basalconditions and within 1 h after EE. Outflow gra-dient increased significantly with EE (13 ± 13to 42 ± 47, P = 0.0001). Under basal con-ditions, shear-induced platelet adhesion (PFA100�) was prolonged in HOCM compared withHCM (264 ± 55 vs. 150 ± 55%, P < 0.0001).VWF-collagen binding activity (VWF:CB) andthe percentage of high molecular weight multi-mers (% HMW) of VWF were significantly re-duced in HOCM compared with HCM (59 ±18 vs. 113 ± 49%, and 4.8 ± 1.3 vs. 11.0 ±1.9% respectively, P < 0.0001). There was nochange in % HMW after EE, but a slight de-crease of PFA 100� and an increase in VWF:Agand VWF:CB (all P < 0.05). There was astrong correlation between either PFA 100� or% HMW at rest and the maximal value of peakgradient during EE (r = 0.72 and r = −0.76respectively, P < 0.0001). The peak gradientduring EE was the only independent predictorof hemostasis alteration at rest. In conclusion,obstruction in HOCM leads to an impairmentof primary hemostasis. Primary hemostasis im-pairment at rest is highly predictive of the max-imal value of peak gradient during exercise.

Effect of exercise on non-enzymatic antioxi-dant status in professional cyclists. J. Medelli,J. Lounana, J.J. Menuet, F. Messan, Z. Cordero-MacIntyre (CHU Amiens, Amiens, France).

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The objective is to evaluate the impact of maxi-mal short duration exercise on oxidative stressand the relationship between the plasma an-tioxidant status, serum lipid radical levels andaerobic performance. Twenty-four professionalmale cyclists performed incremental exerciseon a bicycle ergometer until exhaustion. Cu, Zn,Se, α-tocopherol,VitA, β-carotene and Thio-barbituric Acid Reactive Substances (TBARs)were measured before/after exercise. Hgb andHct were measured to calculate plasma volumechange. The non-parametric Wilcoxon test wasused for comparison before/after exercise andthe Spearman test was used for correlations.Values of P < 0.05 are significant. At rest,plasma concentrations of Vit A, α-tocopherol,β-carotene and Se are higher than normal in 75,54, 32 and 61% of the subjects. TBARs arepositively correlated with VO2max (r = 0.44)and anaerobic threshold VO2 (r = 0.49), Znand Se with anaerobic threshold power (r =0.41 and 0.40). There was a significant dropin Vit A (P < 0.05), β-carotene (P < 0.05),α-tocopherol (P < 0.01) and Se (P < 0.01)but no change in Zn, Cu and TBARs after ad-justment for plasma volume change after exer-cise. Change in Vit A was positively correlatedwith power and all biological parameters (ex-cept TBARs). In conclusion, these results showa decrease of non-enzymatic antioxidants afterexercise and suggest an improved anti-oxidantstatus induced by training.

Expression of Hsp70 in the serum and inmononuclear cells and modification of thephysiological parameters during enduranceexercise. I. Mrizak, F. Slama, I. Ben Cheikh, W.Ben Turkia, Z. Tabka, A. Zbidi (Laboratory ofPhysiology and Functional Explorations, Fac-ulty of Medicine of Sousse, Av. Med El Karoui,4000 Sousse, BP 126, Tunisia).

The study sample was composed of two groups:trained and sedentary subjects. The protocol ofeffort comprised two visits: the first was the de-termination of maximum oxygen uptake. Thesecond visit was that of a rectangular test tofollow the tolerance to endurance exercise (onehour of running with 65% of the maximum oxy-gen consumption) of the two groups accord-

ing to the expression of Hsp70 in systemic cir-culation and the mononuclear cells of blood.Besides Hsp70, other biochemical parameters(lactic acid, creatin phosphokinase CPK, urea)were analysed during the second visit. The firstvisit indicated that the trained subjects had alevel of activity definitely higher than that ofthe sedentary subjects. The second visit showedthat the trained group presented biochemicaldisturbances due to a peripheral tiredness ex-pressed by higher rates of lactic acid at restcompared to the sedentary subjects. In addition,the rates of CPK were maintained high, exceed-ing the standards all along the second visit. Thisunexpected particular situation of the subjectsinvolved seems to influence the expression ofserum and mononuclear Hsp70, which resultedin higher rates in the latter compared to thesedentary subjects. So serum and mononuclearHsp70 of blood can be a tool for the early detec-tion of peripheral tiredness, before the subjectreaches the symptoms revealing a confirmed in-stallation of tiredness which can lead to a fall ofperformance.

Bone mineral density in young Tunisiansoccer players. A. Nebigh, H. Rebai, M.Elloumi, Y. Trabelsi, I. Tarhouni, Z. Tabka,S. Sellami (Laboratory of Physiology andFunctional Explorations, Faculty of MedicineSousse, Tunisia).

We purpose to evaluate the effect of the prac-tice of soccer on bone mineral density dur-ing growth in prepubertal boys. Forty-eightsubjects, prepubertal boys (Tanner stage (2–4) at the start of the study), took part in thisstudy. A series of 25 young soccer players(age: 13.1 ± 0.3 y) trained from 8 to 10 hper week. The control group was formed of23 subjects (age: 12 ± 3.7 y) and did notpractise any extra scholar sport. The propor-tion of CTX (cross labs resorption marker) wascarried out by an immunological technique.The body composition, bone mineral density(BMD) and bone mineral content (BMC) weremeasured by dual energy X-ray absorptiometry(DEXA). Concerning the parameters of bodycomposition, we did not find a difference be-tween young soccer players and the controls.

330 Abstracts

The tendency observed between the values ofCTX for soccer players (2.26 ± 0.52 ng.mL−1)and controls (2.14 ± –0.69 ng.mL−1) was notsignificant. However, the values of BMD weresignificantly higher in the soccer players com-pared with those of the controls. The same sig-nificance was verified for values for whole bodyBMC (P < 0.001). In conclusion, these resultssuggest that soccer, which is a weight bearingphysical activity, has a beneficial effect on bonecontent and density acquisition especially dur-ing growth.

Experimental hypothyroidism and aortic al-terations in Psammomys obesus. S. Neggazi,N. Hamlat, Y. Benazzoug, M. Ardjoun, S.Chaïb, S. Aouichat-Bouguerra (Nutrition andMetabolism laboratory, FSB, USTHB, PO Box32, 16111 El Alia Algiers, Algeria).

Atherosclerosis pathogenesis is complex be-cause of its multifactorial characteristic. Hy-pothyroidism is one of the factors implicated.For our study, we used 2 groups of animals:Psammomys obesus and Rattus norvegicus. Ineach group, rats were rendered hypothyroid byaddition of 0.03% of Carbimazole/day/animalto their drinking water during a period of5 months in Psammomys obesus and 11 monthsin Rattus norvegicus; control rats were givenplain water. Hypothyroidism estimated by TSHmeasurement performed on Rattus norvegicusat the fifth month, showed an increase of 2133%in the experimented animals vs. their corre-sponding controls. The electrophoretic profileanalysis of lipoproteins revealed an increaseof 66.5% of VLDL-LDL and a decrease of92.7% of HDL. However in Rattus norvegi-cus, few variations were shown. The histolog-ical examination of the thoracic aorta showedthat experimental hypothyroidism induced bythe chronic administration of Carbimazole ledto structural alterations (intima thickness andmedia disorder). At the end of our experimenta-tion, the in vitro study of aortic smooth musclecells (SMC) of hypothyroid animals, revealedan increase in proliferation rate, which reached135% in Psammomys obesus and 68% in Rat-tus norvegicus. These results suggest the impli-

cation of hypothyroidism in the development ofthe atherosclerosis process.

Effects of hyposmotic shock on ATP re-lease in turbot (Scophthalmus maximus) hep-atocytes. H. Ollivier, K. Pichavant, E. Puill-Stéphan, C. Goanvec, M. Theron, V. Maxime,P. Calves, S. Roy, L. Nonnotte, G. Nonnotte(Unité de Physiologie Comparée et Intégrative,UFR Sciences et Techniques, 6 Av. Le GorgeuCS 93837, 29238 Brest Cedex 3, France).

Contribution of purinergic signalling to theregulatory volume decrease (RVD) processwas examined in isolated hepatocytes of tur-bot (Scophthalmus maximus), a marine flat-fish. Hyposmotic stress induces ATP releasefrom cells which stimulates membrane puriner-gic receptors and triggers cascades of intra-cellular events. RVD is partially preventedby ATP diphosphohydrolase apyrase and P2receptor antagonist suramine. Cellular shrinkis triggered by ATP added to an isos-motic medium. cAMP potentiates osmosensi-tive ATP trafficking as adenylyl cyclase ac-tivator forskolin increases nucleotide release.By contrast, verapamil, a mdr1 P-glycoproteininhibitor, and gadolinium, a stretch-activatedchannels inhibitor, failed to prevent the mech-anism, excluding involvement of such proteinsin nucleotide export. Hyposmotic swelling ofhepatocytes elicits a transient rise in cytoso-lic calcium concentration ([Ca2+]i) which couldcontribute to ATP release since the calciumionophore ionomycin caused nucleotide effluxunder isosmotic conditions and the calciumchelator EGTA abolished ATP release underhyposmotic conditions. These data provide thefirst evidence of a volume-sensitive ATP sig-nalling aimed at volume constancy of a marineteleost fish cell type.

Renal alterations induced by injected me-thionine in rabbit Oryctolagus cuniculus. K.Othmani-Mecif, L. Khedis, Y. Benazzoug (Ex-tracellular Matrix, BCM, FSB, USTHB, BP 32,16111, El Alia Algiers, Algeria).

Methionine, an essential amino acid impor-tant in the composition of any diet becomes

Physiology Society Symposium 331

a considerable factor of vascular risk when itis introduced in high concentration. The aimof this work consisted in studying the effectof the injection, by sub-cutaneous way, of thisamino acid on the uremia and proteinemia andon the histo-morphometry of the rabbit kid-ney. The experimentation was carried out on lo-cal female rabbits which received during onemonth, 121 mg of methionine.kg−1 of bodyweight per day. The untreated animals receivedphysiological water under the same conditions.The follow-up of uremia showed an elevationat day 15 of treatment followed by a fall atthe end; proteinemia increased slowly until the7th day and then became normal until day 30.The renal histology of treated rabbits showeda thickening of the mesangium, a widening ofthe blood capillaries and a deposit of conjunc-tive material between the tubes in the medullaryzone. Comparatively to the untreated rabbit, themorphometric study indicates a reduction in thecorpuscule axes (P < 0.05) with a marked in-crease in the glomerular room (P < 0.0001).The height of the collector and the circum-vented distal tubes decreased to a significant de-gree (P < 0.01) whereas the cells of the thinportion of the Henle tube seemed unchanged.

Opening of connexin40, 43 and 45 hemichan-nels expressed in CHO cells by ATP deple-tion. I. Plante, D. Fournier, L. Gailis, P. Daleau(Institut de Cardiologie de Québec, HôpitalLaval, 2725 chemin Ste-Foy, Ste-Foy, Canada).

Connexons of adjoining cells dock to form gapjunction channels which allow the passage ofions and small molecules. They are composedof six transmembrane protein subunits calledconnexins (Cx). Cx belong to a multigene fam-ily of ∼ 20 members. The heart expresses theCx40, 43 and 45 isoforms. It has been shownthat connexons may function as transmembraneion channels. This study was designed to in-duce connexon opening by intracellular ATPdepletion. cDNA of Cx40, 43 and 45 were in-dividually transfected in CHO cells. We usedthe patch-clamp technique and a voltage rampprotocol (from –80 to +60 mV in 1.5 s) for mea-surement of ionic currents. In untreated trans-fected cells, the normalised slopes of current in-

duced by voltage ramps were minimal (0.04 ±0.005 nA/V/pF). The presence of 2 mM glu-cose, 2 mM 2-deoxyglucose and 10 µM an-timycin A induced an opening of the connex-ons. The average slopes for Cx40, Cx43 and45 and controls (i.e. non-transfected cells) were1.14 ± 0.58, 1.09 ± 0.35, 0.35 ± 0.06 and 0.08 ±0.04 respectively (n = 3/group). We also testedthe effect of 5 mM 2-deoxyglucose +2 mM glu-cose on Cx45; the slope was 0.94 ± 0.44 com-pared to 0.07 ± 0.02 for controls (n = 3/group).Low-ATP induced increase in cell permeabil-ity was confirmed using the fura2 fluorescencetechnique; an accumulation of Ca2+ was onlyobserved in the transfected cells. In conclu-sion, we showed that intracellular ATP deple-tion is able to induce opening of connexonsformed from Cx40, 43 and 45. Thus, openingof hemichannels is likely to develop during car-diac ischemia and to be involved in associatedelectrical abnormalities.

Excess of methionine induces heart dam-age. L. Raaf, N. Ben Ahmed, K. HadjZiane, M. Rahim, S. Aouichat-Bouguerra, Y.Benazzoug (Laboratoire Matrice Extracellu-laire. FSB, USTHB. BP 32 El Alia, Bab Ezzour,Alger, Algéria).

A number of statistic and epidemiologic studieshave shown the increase of cardiovascular dis-eases risk with hyperhomocysteinemic subjects.These suffer from coronary, cerebral, periphericvessel injuries and thoracic atherosclerosis. Asvessels, Hyperhomocysteinemia induces dam-ages in several other organs like the liver, kid-ney, brain and heart. Our results report al-teration of heart histomorphometric propertiesin experimental hyperhomocysteinemic Wis-tar rats. Chronic methionine administration at140 mg.kg−1 of weight body/day for 6 monthscaused collagen, PAS material and cell ac-cumulation in endocardic space. Connectivecomponent deposits were furthermore revealedin the myocardium between myocyts but essen-tially around vessels. This histological data cor-roborate with morphometric results which indi-cate thickness of endocarde and vessels wall.

Force-velocity of extensors and flexors trunkmuscles under isokinetic conditions. M.

332 Abstracts

Ripamonti, A. Rahmani, D. Colin (Laboratoiredes APS, Université du Maine, Av. Olivier Mes-siaen, 72085 Le Mans Cedex 9, France).

The aim of this study was to establish a Force-Velocity relationship for the trunk flexor mus-cles on the one hand, and the trunk extensormuscles on the other hand, under isokinetic con-ditions. To the authors’ knowledge, no studyhas dealt with this subject. Nine healthy sub-jects (26 ± 11 years, 75 ± 15 kg, and 176 ±19 cm) performed a series of flexion and a se-ries of extension on a Biodex dynamometer at6 various angular velocities 120, 105, 90, 75,60 and 45.s−1 (2.09, 1.83, 1.57, 1.31, 1.05 and0.78 rad.s−1). The test demonstrated that, to allthe subjects, the Force-Velocity relationshipsobtained were linear for the flexor muscles (P <0.01; 0.85 < r2 < 0.98) and polynomial of thesecond order (P < 0.03 and 0.67 < r2 < 0.98)for the extensor muscles of the rachis. Severalhypotheses are advanced to explain this differ-ence. The main cause seems to be fatigue.

Sensory-specific satiety: could it be dimin-ished by a change in alimentary olfacto-gustatory stimulation in humans? M. Romer,J. Lehrner, V. Van Wymelbeke, T. Jiang, L.Deecke, L. Brondel (Centre des Sciences duGoût, 15 rue Hugues Picardet, 21000 Dijon,France).

Alimentary sensory pleasure is an importantfactor in ingestive behavior. Renewal of olfacto-gustatory pleasure by introducing new foodsor through seasoning the previously consumedfood might increase intake. To find out whethersensory-specific satiety (SSS) for a food couldbe modulated, either by introducing a novelfood or by a modification of sensory stimu-lation via minor manipulations upon the foodjust eaten. One hundred eighty healthy subjectswere distributed over 3 experiments involvingintake of one out of 6 fresh foods (cucumber,tomato, pineapple, banana, peanut, pistachio).Before and after intake of the olfactorily chosenfood, blindfolded subjects rated the foods onthe following: Olfactory Pleasure (OP), SpecificAppetite (SA) and Stimulus-Induced Salivation(SIS). Exp. 1: one chosen food was repeatedlypresented orthonasally and rated before and af-

ter it was eaten. Exp. 2: a second food was ol-factorily chosen and ingested after the first one.Exp. 3: the same food was offered again af-ter seasoning it. In Exp. 1, 2 min after inges-tion, food-intake was limited by SSS and OP,SA, SIS were correlated among each other foreaten and uneaten foods. In Exp. 2, OP for un-eaten foods was significantly (P < 0.01) in-creased after ingestion of a chosen food to spe-cific satiety. In Exp. 3, when the food just eatenwas seasoned, OP increased (P < 0.01) and ledto additional intake (80% of the first intake).These results suggest that SSS is not a stablephenomenon, since it was reduced after intro-duction of a new flavor or after seasoning aningested food. This could explain how food va-riety leads to over-consumption.

Oral epithelial cells are involved in in-nate immunity against fungal (Candida al-bicans) infection through antimicrobial pep-tides β-defensins. M. Rouabhia, K. Savignac,J. Chakir (Faculté de médicine dentaire, Univer-sité Laval, Québec, Canada).

Epithelial cells may be involved in innate im-munity against bacterial and yeast infections viaa number of broad-spectrum antimicrobial pro-teins such as human β-defensin-1 (HBD-1) andHBD-2. The aim of this study was to investi-gate the effect of C. albicans on the produc-tion of HBD-1 and HBD-2 by oral epithelialcells and to evaluate the effect of these pro-teins on C. albicans growth and morphology.First, oral epithelial cells were infected with105 C. albicans for 2, 4, 8, and 24 h. West-ern Blot testings were performed at the endof each infection time point using proteins ex-tracted from the cells. Second, C. albicans wascultured in the presence of HBD-1 or HBD-2and later seeded on agarose plates. These wereincubated for 3 and 6 h and their colonies wereassessed. Finally, C. albicans was cultured inthe presence of HBD-1/HBD-2. Yeast was lateradded to a medium containing 20% of bovineserum. The morphological changes were fol-lowed at 1, 2, 3 and 4 h using an optical mi-croscope. C. albicans modulated the productionof HBD-1 and HBD-2. HBD-1 and HBD-2 in-hibited the growth and morphological changes

Physiology Society Symposium 333

of C.albicans. This inhibition was greater whenC. albicans was in contact with the HBD for alonger period of time (6 h). The important effectwas obtained with HBD-2. This study suggeststhat oral epithelial cells are involved in C. albi-cans growth and morphological changes controlvia antimicrobial peptides HBD-1 and HBD-2.

Supported by the FRSQ and NORTH.

ACE inhibition and endurance exercise ca-pacity in type 1 diabetes mellitus. O. Rouyer,J. Zoll, F. Daussin, P. Helms, F. Thaveau, T.Chataigneau, V. Schini-Kerth, C. Damgé, F.Piquard, B. Geny (Laboratoire de Physiologieet Explorations Fonctionnelles, CHRU, 1 placede l’Hôpital, 67000 Strasbourg, France).

The objective is to determine whether ACEiimproves diabetic rat exercise capacity throughan improvement in skeletal muscle metabolismand/or endothelial function. Wistar Rats weredivided into three groups: control (CTL), di-abetics (D), diabetics with perindopril (DP:6 weeks, 2 mg.kg−1.day−1). Type 1 diabeteswas induced with intravenous administrationof streptozotocin (65 mg.kg−1), 8 months be-fore perindopril treatment. After habituationon a treadmill, an exhaustive endurance test(10 cm.s−1) was then performed. A week later,endothelial function was determined by tho-racic aorta relaxation together with mitochon-drial oxidative capacities (Vmax) in perme-abilised fibres of gastrocnemius muscle. D andDP presented enhanced plasma glucose andbody weight, compared with CTL. D presentedwith hypertension (158 ± 12 mmHg) vs. DP(129 ± 4 mmHg) and CTL (130 ± 6 mmHg),P = 0.02. Exercise capacity severely de-creased in D (28.7 ± 2.1 min) and DP (8.32 ±1.7 min), compared to CTL (91.5 ± 2.2 min),P < 0.001. Similarly, Vmax decreased in D(4.34 ± 0.83 µmol d’O2.min−1.g−1) and DP(4.34 ± 0.85 µmol d’O2.min−1.g−1) vs. CTL(10.32 ± 0.67 µmol d’O2.min−1.g−1), P <0.001. In DP, exercise capacity was correlatedwith Vmax (r = 0.79, P = 0.033), withendothelial dependant relaxation being identi-cal in the three groups. In conclusion, skeletalmuscle metabolism alterations could partly ex-plain the severe exercise capacity impairment

observed in diabetes mellitus rats. The unex-pected exercise capacity decrease in the DPgroup could be related to their blood pressurenormalisation and/or diabetes duration.

Results of the “défi” 4S (Sport-Santé/Séden-tarité-Surpoids) network. G. Scetbon, J.Pouzols, D. Thibaud, G. Connault-Levaï, E.Conte, A. Duvallet, V. Lebar (Centre médico-sportif, Av. Jean Moulin, 77176 Savigny-le-Temple, France).

In September 2003, a health-care network wascreated in Savigny-le-Temple (Seine-et-Marne)at the initiative of different public organiza-tions: Conseil Général, DDJS, DRDJS, Inspec-tion Académique, Conseil Régional, CDOSand CROSIF. At the center of this networkis the “Centre Médico-Sportif” which acts asa link between the medical professionals in-volved (private doctors, hospital doctors, schoolmedicine practitioners and PMI) and actors ofsports activities (clubs and associations). Thenetwork is in charge of organizing the medi-cal support and sports activities for overweightchildren and adolescents. After 18 months ofnetwork activity, 78 patients had been fol-lowed during more than 400 visits; obesity hadbeen diagnosed by school medicine doctors andnurses for 26% of these patients, by private doc-tors (general practitioners and pediatricians) for26% and by the “Centre Médico-Sportif” for21%. Patients were 6 to 16 years of age at thetime of inclusion and the mean age at dectec-tion was 11 years and 5 months. The studypopulation included 62% of girls and 38% ofboys. The patients (43%) were initially diag-nosed with class 2 obesity, 47% with class 1obesity and 10% as overweight. During thisprogram of medical and sports activities follow-up, 87 patients participated in one sports ac-tivity on an annual basis, 7 patients were alsofollowed in the Melun hospital for paraclinicaltests or in case of difficulties in their medicalmanagement. Participation in the program wasgood with only 10 children dropping out of theprogram, 3 of them because they moved. Con-sidering weight and height development, BMIwas reduced or stabilised in 83% of the patients

334 Abstracts

and augmented in 17%. In our opinion, these re-sults justify the pursuit of this multidisciplinaryprevention program.

Effectiveness of counselling overweight andobese patient in the “défi 4S” network (Sport-Santé/Sédentarité-Surpoids). G. Scetbon, J.Pouzols, A. Duriez, J.J. Combourieu, V. Lebars,A. Duvallet (Centre médico-sportif, Av. JeanMoulin, 77176 Savigny-le-Temple France).

Obesity is a complex multi-factorial diseasewith prevalences significantly associated withage, sedentary lifestyle and nutritional educa-tion. Prevention during childhood should beconsidered a priority, since there is a risk ofpersistence in adulthood. Intervention childrenshowed high scores of efficiency with behaviourmodification programmes for healthy eatingand physical activity. Management of obesitywill require a comprehensive range of effec-tive strategies. The programme was intendedto influence physical activity behaviour and di-etary behaviour. Physical activity, by increas-ing energy expenditure had a positive role inreducing fat storage and adjusting balance inoverweight patients. The philosophy is aimedat linking all actors of this challenge of a pub-lic health problem. The “défi 4S” network wascreated in 2003 with public organisations (villede Savigny-le-Temple, Conseil Général de laSeine-et-Marne (77), Conseil Régional d’Île-de-France), government (DRDJS Paris-Île-de-France, DDJS77), general, national educationand sports medicine doctors, and clubs or or-ganisations of sports (CDOS77 et CROS Île-de-France). Overweight children were detectedby measuring BMI (body mass index). Theywere classified according to WHO. Identifiedas “overweight or obesity class I and class II”(BMI < 40), they were addressed to sportsmedicine practitioners to discuss increasing ac-tivities and decreasing of improper eating be-haviour. They decided appropriate goals. Thepatients identified as “obesity classe III” (BMI> 40) were followed by a pediatrician of theMelun general hospital. The first patient was in-cluded in November 2003. From this date tillnow, 135 children have been recruited; all were

“less active or inactive”. Seventy accepted vol-untary to participate (52%). Participation wasvery good; only 6 patients stopped. They prac-tised 16 kinds of sports, and several for some(basketball 18, swimming and badminton 12,School of sports 10, Athletics 9, dance 5, foot-ball 4, table-tennis, cycling and gymnastics 3,handball and judo 2, tennis, karate, boxing andhorse-riding 1). The exercise specialists werevolunteers having specific training in the “défi4S” network before they received the first over-weight sportsman.

Abnormal SpO2 in obese adolescents: as-sessment by functional tests and impact ofweight reduction. J.M. Sène, M.L. Frelut,G. Pérès (Physiologie du Sport, CHU Pitié-Salpètrière, AP-HP 75013 Paris, CTP Mar-gency et Hôpital St-Vincent-de-Paul AP-HP75014 Paris, France).

Aerobic conditions are very important to re-store in obese subjects. SpO2 was measured atrest and during ventilatory tests in obese ado-lescents (OB) before and after a weight reduc-tion programme (WRP). 11OB (13.7 ± 1.3 y;BMI = 42.3 ± 4.5 kg.m−2) were compared to11 controls (C) (13.8 ± 1.0 y; BMI = 19.1 ±1.9 kg.m−2, P < 0.0001) before and after a mul-tidisciplinary WRP (BMI = 32 ± 4.5 kg.m−2,P < 0.0001) SpO2 (Nellcor� saturometer)and heart rate (HR, Polar�) were continuouslyrecorded at rest and during an apnea (AT) and ahyperapnea test (HT) of 15 s each. SpO2 were≥ 97% in all C and 7/11 OB (normosaturated:Nsat) and < 97% in the 4/11 remaining OB(subsaturated: Ssat). After the WRP, SpO2 was≥ 97% in all subjects. The more obese were theadolescents, the lower were their SpO2. SpO2

decreased < 94% during AT in 3/11 OB, beforebut in none after the WRP nor in C subjects.SpO2 increased in all subjects up to ≥ 98% dur-ing the AT, followed by a decrease under theresting value, starting later in Ssat adolescents(102 ± 43 s) than in the Nsat adolescents (51 ±13 s) and the C group (22 ± 6 s). SaO2 lev-els at rest were heterogeneous in OB adoles-cents, lower than in C adolescents and got worseduring an AT. The slower response after SpO2

variations suggests the existence of significant

Physiology Society Symposium 335

differences in the ventilation regulatory mecha-nisms in OB. In conclusion, the 15 s HT appearsto be an appropriate tool in order to detect ab-normal ventilatory responses in OB. Our WRPleads to significant SpO2 improvement and ap-nea tolerance.

Grant from INSERM.

Antioxidant properties of rosuvastatin wereassociated with an ischemia-reperfusion car-dioprotective effect in normotensive rats. P.Sicard, B. Lauzier, S. Delemasure, C. Vergely,L. Rochette (LPPCE, IFR No. 100, Facultiesof Medicine and Pharmacy, 7 Bd Jeanne d’Arc,21000 Dijon, France).

The aim of this study was to appreciate theconsequence of a chronic treatment of nor-motensive (WKY) and hypertensive (SHR) ratswith rosuvastatin on (i) isolated heart func-tion under conditions of ischemia-reperfusionand (ii) oxidative stress reperfusion levels. At10 weeks of age, SHR and WKY rats weregiven or not rosuvastatin (per os, 10 mg.kg−1

daily for 3 weeks). Systolic blood pressure wasassessed every week. Hearts were isolated, per-fused (Langendorff) and subjected to 30 min ofglobal ischemia followed by 30 min of reper-fusion. Functional parameters (coronary flow,left ventricular developed pressure, heart rate)were measured. Reactive oxygen species (ROS)produced during reperfusion were quantified byelectron spin resonance spectroscopy using aspin probe (CP-H, 1 µM). An oxidative flu-orescent probe, dihydroethidium was used tolocalise superoxide anion production in heartslices. In our experimental conditions, 3 weeksof treatment with rosuvastatin did not lowerplasma cholesterol levels, but reduced arte-rial blood pressure in SHR rats (–18 mmHg,P < 0.01). Before ischemia and during reper-fusion, cardiac functional parameters deterio-rated in SHR as compared to WKY hearts. InWKY but not in SHR, rosuvastatin treatmentsignificantly lessened by 50% the post-ischemiccontracture enhanced left ventricular developedpressure (P < 0.05) and lowered ROS re-lease during reperfusion (P < 0.05). Fluores-cent quantification of superoxide production inheart slices showed a reduction of coronary ar-

teries staining. In conclusion, chronic treatmentwith rosuvastatin of normotensive rats enhancesmyocardial recovery after ischemia-reperfusionand lessens reperfusion-associated free radicalproduction. However, if rosuvastatin can de-crease arterial blood pressure in SHR, the my-ocardial protective effects observed in WKY areno longer present in this hypertensive strain ofrats. It is possible that SHR presents a myocar-dial resistance to the pleiotropic effects of rosu-vastatin.

Biventricular stimulation in female patientswith chronic heart failure: evaluation offunctional parameters after 3 months. J.Siegelová, M. Novák, P. Vank P, J. Jancík, J.C.Eicher, J.E. Wolf, L. Mífková, L. Kožantová,H. Svacinová, P. Dobšák, J. Vítovec (Dept.of Functional Diagnostics and Rehabilitation,St. Anna Faculty Hospital Brno, Faculty ofMedicine, Masaryk University, Pekarská 53,656 91 Brno, Czech Republic).

The objective is this study was aimed at theevaluation of the influence of biventricular stim-ulation on oxygen uptake and maximal work-load in group of female patients with chronicheart failure (CHF) practicing normal activities.A group of female patients (n = 7; mean age69.0 ± 7.2 years) with dilative cardiomyopa-thy and CHF with implanted biventricular pace-maker (BiV PM) was evaluated. All subjectsunderwent a spiroergometric test (to symptom-limited maximal level) and 2D echocardiogra-phy 14 ± 10 days before BiV PM implanta-tion; the same tests were repeated after 3.0 ±0.4 months. The following parameters weremeasured: maximal symptom-limited oxygenuptake (VO2SL and VO2SL.kg−1), symptom-limited maximal workload (WSL) and left-ventricle ejection fraction (LVEF). All thesubjects included practiced only standard nor-mal activities. A significant increase of WSL

(*64.0 ± 10.2 W vs. 57.0 ± 7.0 W at base-line; *P < 0.05) and LVEF (*28.0 ± 5.8% vs.24.0 ± 3.5% at baseline; *P < 0.05) valueswere observed after 3 months of BiV PM im-plantation. The statistical analysis of the val-ues of VO2SL (1054.0 ± 183.7 mL.min−1 vs.997.0 ± 234.2 mL.min−1 at baseline) and of

336 Abstracts

VO2SL.kg−1 (16.6 ± 3.05 mL.min−1.kg−1 vs.15.7 ± 2.65 mL.min−1.kg−1 at baseline) didnot show statistical significance. In conclusion,3 months of biventricular stimulation improvedthe functional capacity in female patients withCHF, it was demonstrated by the significant in-crease of the values of maximal workload andLVEF. Although the evaluation of the maximaloxygen uptake did not show statistical signif-icance, a clear tendency to improvement waspresent.

Supported by grants IGA MZ CR NR-7893-3 andMSM 0021622402.

Effects of the playing position and increas-ing test load on the anaerobic performancesin Algerian soccer players. Z. Taoutaou, H.Bounekar, M. Arafa, A. Baz (Laboratoire desAPM, INFS/STS de Dely-Ibrahim, BP 71 El-Biar, Alger, Algeria).

The purpose of the study was to comparethe anaerobic performances in Algerian soccerplayers based on the playing position and to as-sess the effect of increasing test load on anaer-obic peak power (Wx; Wx.kg−1) and capac-ity (Wan; Wan.kg−1). The study was conductedon 34 soccer players from the national juniorteam (16 defenders, 8 midfielders, 10 forwards).Their means (± SEM) for age, body mass andheight were 18.5 ± 0.96 years; 67.7 ± 1.06 kg;and 175 ± 8 cm, respectively. All subjects per-formed 30-s cycle sprint (Wingate anaerobictest) against a load of 75 g.kg−1 (W75) bodyweight, vertical jump (H), 10-m (T10) and 50-m(T50) sprints. In addition, 13 soccer playersperformed the Wingate anaerobic test againsttwo other resistances (90 g.kg−1 (W90) and110 g.kg−1 (W110) body weight). The meanvalues of anaerobic peak power were in de-fenders: 676.5 ± 33 W (9.55 ± 0.33 W.kg−1),midfielders: 575.5 ± 34 W (8.6 ± 0.4 W.kg−1),forwards: 645.5 ± 32 W (9.79 ± 0.3 W.kg−1).During the Wingate test performed at 75 g.kg−1

load, there was no significant difference inanaerobic peak power between players basedon positions, although the capacity expressingin relative values was higher in forwards com-pared to midfielders (P < 0.05). The mean val-ues of H, T10 and T50 were similar between

groups. There was significant differences be-tween W75 and W90 ((Wx, P < 0.01; Wx.kg−1,P < 0.01); (Wan, P < 0.01; Wan.kg−1,P < 0.01)); W90 and W110 (Wx, P < 0.01;Wx.kg−1, P < 0.01) and between W75 andW110 (Wan, P < 0.01; Wan.kg−1, P < 0.01).It was concluded that the peak power measuredduring the Wingate test, vertical jump, 10-mand 50-m performances were not affected by theplaying position.

The non toxicity of mineral elements afteroral administration in the rat. L. Tekaya-ElManoubi, E. Fehri, A. Ayadi, P. Galle (Labo-ratoire de Physiologie, Faculté de Médecine deTunis, 15 rue Jebel Lakhdhar, 1007 Bab Saâ-doun, Tunis, Tunisia).

The chemical toxicity of several mineral el-ements after parenteral administration is wellknown. Among these elements are Indium andespecially Aluminium whose frequent intoxi-cation is linked to its presence in dialysis wa-ter when used for patients treated for chronickidney failure. Its accumulation in the neu-rone lysosomes is responsible for the occur-rence of encephalopathies and its accumulationin the bone for the occurrence of bone deminer-alisation and spontaneous fractures. The aimof this work was to show the behaviour ofthe intestinal mucosa, liver and kidney after asimultaneous oral administration of both alu-minium and indium. Two methods of observa-tion and microanalysis were used: the conven-tional transmission electron microscopy and thesecondary ion mass spectrometry. The resultsshowed that aluminium and indium were selec-tively concentrated in the same lysosomes ofduodenum enterocytes as no soluble phosphateform, so there was no specialised lysosome for agiven element. These precipites were later elim-inated with apoptotic cells in the intestinal lu-men in less than 72 h. The efficiency of thisphenomenon is shown here because of the ab-sence of these elements in the liver and kidney.It is suggested that the duodenum could play animportant role because of the limitation of toxicelement diffusion in the plasma.

Physiology Society Symposium 337

N-3 fatty acids-deficient rats exhibit im-paired acquisition of an olfactory discrimi-nation task. S. Ullah, M. Rialland, F. Datiche,F. Liénard, A. Hichami, J.M. Chardigny, M.Cattarelli, N.A. Khan (UPRES Lipides et Nu-trition, Université de Bourgogne, 6 Bd Gabriel,Dijon, France).

Diets enriched with n-3 polyunsaturated fattyacids (PUFA) n-3 exert beneficial effects inhealth and disease. In order to elucidate therole of dietary n-3 PUFA in olfactory discrim-ination, the rats were fed, for two generations,on a diet which induced in vivo deficiencyin n-3 PUFA contents. The experiments wereperformed on n-3 PUFA-deficient diet (PUFA-DD)-fed rats of the second generation (F2). Thecontrol rats were fed a balanced diet (BD). Therats fed PUFA-DD and BD were submitted toan olfactory discrimination task learning in afour-arm maze where they had to associate oneodour of a pair with a water-reward. The PUFA-DD fed rats showed a slower acquisition of theolfactory discrimination task compared to theBD fed rats. At the end of the conditioning,all the rats were sacrificed and the analysis offatty acid composition in different brain areas(olfactory bulb, hippocampus, cortex piriformand neocortex) was performed. Feeding PUFA-DD to rats resulted in a loss of around 80% ofDHA in total lipids and phospholipids in differ-ent brain areas. The decrease in DHA contentsin PUFA-DD rats is correlated with an increaseof docosapentaenoic acid (22:5 n-6) levels in allthe brain areas of these animals. We also studiedthe expression of phosphorylated proteins (Fos,Egr1, CREB, MAP Kinase) which are involvedin cell signalling. We observed that the expres-sion of these phosphorylated proteins was nothighly significantly different in BD and PUFA-DD rats. At present, we are investigating theexpression of several genes, involved in synap-tic transmission, in different brain areas of theseanimals.

Autonomic function assessed by heart ratevariability in frail elderly people with pos-tural abnormalities and in control subjects.V. Van Wymelbeke, F. Mourey, D. Moreau, M.Buchheit, P. Pfitzenmeyer, L. Brondel (Centre

Européen des Sciences du Goût, 15 rue HuguesPicardet, 21000 Dijon, France).

Heart rate variability (HRV), which is consid-ered to reflect the activity of the autonomic ner-vous system (ANS), has been reported to de-cline with age. The aim of the study was toexplore autonomic nervous activities in olderpatients showing Psychomotor DisadaptationSyndrome (PDS) through 24-h ECG record-ings.The study included a PDS group (14 pa-tients, 84.5 ± 6.9 years) and a control group(13 frail subjects without postural abnormali-ties, 80.6 ± 6.7 years). ANS was assessed us-ing the standard deviation of the all normal R-Rintervals (SDNN), the square root of the meansquared differences of successive R-R inter-vals (RMSSD), the percentage of interval differ-ences of successive R-R intervals greater than50 ms (pNN50), then for spectral analysis usingtotal power (Ptot) and power density in the low-frequency (LF) and high-frequency (HF) bands.SDNN of the PDS group was lower than that ofthe control group both for the day and the nightperiods (P < 0.05) and RMSSD was lower bothfor the 24 h and the night periods (P < 0.05).Total power (Ln Ptot) was lower in the PDSgroup than in the control group for the 24 h,day and night periods (P < 0.05). Values of LnLF and Ln HF were also smaller for the PDSgroup than for the control group for the 24 h,day and night periods (P < 0.05). The decreaseof ANS activity observed in PDS subjects wasthen more important that the alteration found innormal ageing.

Modulation of antioxidant status in alcohol-related diabetes mellitus in Beninese sub-jects. A. Yessoufou, K. Moutairou, A. Girard,M. Fatoké, J. Prost, H. Ahissou, F. Djrolo, G.Avodé, D. Amoussou-Guenou, A. Hichami,N.A. Khan (Université de Bourgogne, Départe-ment de Physiologie, UPRES Lipides et Nutri-tion, Dijon, France).

In the present study, we investigated the antiox-idant status in diabetes mellitus, related or notto alcohol consumption. A total of 38 type 1,48 type 2 and 42 alcohol-related diabetespatients were selected by specialist clinicians

338 Abstracts

from an Insulin Bank (Diabetic Centre) and En-docrinology Department of the Centre NationalHospitalier et Universitaire of Cotonou, Benin(West Africa). Total antioxidant status wasassessed through the oxygen radical absorbancecapacity of the plasma and the determinationof enzymatic and non-enzymatic antioxidantmolecules. Serum triglycerides, total choles-terol and HDL-cholesterol concentrations weredetermined and the lipid peroxydation wasevaluated by specifically measuring thiobar-bituric acid reactive substances (TBARS)assay. Plasma total antioxidant capacity wasmore decreased in alcohol-related diabetespatients than in type 1 and type 2 dia-betes patients, regardless of the complications

(retinopathy and renal failure). Plasma vitaminE concentrations were significantly decreasedwhereas those of vitamin C increased in all di-abetic patients compared to the controls, irre-spective of the complications. In addition, su-peroxide dismutase and glutathione peroxidaseactivities were reduced in all patients (type 1,type 2 and alcohol-related), irrespective of thecomplications. Glutathione reductase activitywas diminished in type 1 and alcoholic, but notin type 2, diabetic patients. Excessive alcoholconsumption appears as an oxidative aggravat-ing factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles type 1 dia-betes as far as the antioxidant parameters areconcerned.

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