A mathematical model to describe fat oxidation kinetics during graded exercise.

PURPOSE: The purpose of this study was to develop a mathematical model (sine model, SIN) to describe fat oxidation kinetics as a function of the relative exercise intensity [% of maximal oxygen uptake (%VO2max)] during graded exercise and to determine the exercise intensity (Fatmax) that elicits maximal fat oxidation (MFO) and the intensity at which the fat oxidation becomes negligible (Fatmin). This model included three independent variables (dilatation, symmetry, and translation) that incorporated primary expected modulations of the curve because of training level or body composition. METHODS: Thirty-two healthy volunteers (17 women and 15 men) performed a graded exercise test on a cycle ergometer, with 3-min stages and 20-W increments. Substrate oxidation rates were determined using indirect calorimetry. SIN was compared with measured values (MV) and with other methods currently used [i.e., the RER method (MRER) and third polynomial curves (P3)]. RESULTS: There was no significant difference in the fitting accuracy between SIN and P3 (P = 0.157), whereas MRER was less precise than SIN (P < 0.001). Fatmax (44 +/- 10% VO2max) and MFO (0.37 +/- 0.16 g x min(-1)) determined using SIN were significantly correlated with MV, P3, and MRER (P < 0.001). The variable of dilatation was correlated with Fatmax, Fatmin, and MFO (r = 0.79, r = 0.67, and r = 0.60, respectively, P < 0.001). CONCLUSIONS: The SIN model presents the same precision as other methods currently used in the determination of Fatmax and MFO but in addition allows calculation of Fatmin. Moreover, the three independent variables are directly related to the main expected modulations of the fat oxidation curve. SIN, therefore, seems to be an appropriate tool in analyzing fat oxidation kinetics obtained during graded exercise.

Carcinoembryonic antigen (CEA) in non digestive cancerous and normal tissues.

Carcinoembryonic antigen (CEA), immunologically identical to CEA derived from colonic carcinoma, was identified and purified from perchloric acid (PCA) extracts of bronchial and mammary carcinoma. CEA extracted from bronchial and mammary carcinoma was quantitated by single radial immunodiffusion and was found to be in average about 50-75 times less abundant in these tumors than in colonic carcinoma. CEA could also be detected in one normal breast in lactation and at lower concentrations in normal lung (1000-4000 times lower than in colonic carcinoma). The small amounts of CEA present in normal tissues are distinct from the glycoprotein of small mol. wt showing only partial identity with CEA, that we recently identified and extracted in much larger quantities from normal lung and spleen. The demonstration of the presence of CEA in non digestive carcinoma by classical gel precipitation analysis suggests that the CEA detected in the plasma of such patients by radioimmunoassay is also identical to colonic carcinoma CEA. Our comparative study of plasma CEA from bronchial and colonic carcinoma, showing that CEA from both types of patient has the same elution pattern on Sephadex G-200 and gives parallel inhibition curves in the radioimmunoassay, is in favor of this hypothesis. However, it should not be concluded that all positive CEA radioimmunoassay indicate the presence of an antigen identical to colonic carcinoma CEA. A word of warning concerning the interpretation of radioimmunoassay is required by the observation that the addition of mg amounts of PCA extract of normal plasma, cleared of CEA by Sephadex filtration, could interfere in the test and mimic the presence of CEA.

Effects of hyperglycemia on glucose metabolism before and after oral glucose ingestion in normal men.

The plasma glucose excursion may influence the metabolic responses after oral glucose ingestion. Although previous studies addressed the effects of hyperglycemia in conditions of hyperinsulinemia, it has not been evaluated whether the route of glucose administration (oral vs. intravenous) plays a role. Our aim was to determine the effects of moderately controlled hyperglycemia on glucose metabolism before and after oral glucose ingestion. Eight normal men underwent two oral glucose clamps at 6 and 10 mmol/l plasma glucose. Glucose turnover and cycling rates were measured by infusion of [2H7]glucose. The oral glucose load was labeled by D-[6,6-2H2]glucose to monitor exogenous glucose appearance, and respiratory exchanges were measured by indirect calorimetry. Sixty percent of the oral glucose load appeared in the systemic circulation during both the 6 and 10 mmol/l plasma glucose tests, although less endogenous glucose appeared during the 10 mmol/l tests before glucose ingestion (P &lt; 0.05). This inhibitory effect of hyperglycemia was not detectable after oral glucose ingestion, although glucose utilization was increased (+28%, P &lt; 0.05) due to increased nonoxidative glucose disposal [10 vs. 6 mmol/l: +20%, not significant (NS) before oral glucose ingestion; +40%, P &lt; 0.05 after oral glucose ingestion]. Glucose cycling rates were increased by hyperglycemia (+13% before oral glucose ingestion, P &lt; 0.001; +31% after oral glucose ingestion, P &lt; 0.05) and oral glucose ingestion during both the 6 (+10%, P &lt; 0.05) and 10 mmol/l (+26%, P &lt; 0.005) tests. A moderate hyperglycemia inhibits endogenous glucose production and contributes to glucose tolerance by enhancing nonoxidative glucose disposal. Hyperglycemia and oral glucose ingestion both stimulate glucose cycling.

Photodynamic therapy enhances liposomal doxorubicin distribution in tumors during isolated perfusion of rodent lungs.

BACKGROUND: Photodynamic therapy (PDT) at low drug-light conditions can enhance the transport of intravenously injected macromolecular therapeutics through the tumor vasculature. Here we determined the impact of PDT on the distribution of liposomal doxorubicin (Liporubicin™) administered by isolated lung perfusion (ILP) in sarcomas grown on rodent lungs. METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the left lung of Fischer rats. Treatment schemes consisted in ILP alone (400 μg of Liporubicin), low-dose (0.0625 mg/kg Visudyne®, 10 J/cm(2) and 35 mW/cm(2)) and high-dose left lung PDT (0.125 mg/kg Visudyne, 10 J/cm(2) and 35 mW/cm(2)) followed by ILP (400 μg of Liporubicin). The uptake and distribution of Liporubicin in tumor and lung tissues were determined by high-performance liquid chromatography and fluorescence microscopy in each group. RESULTS: Low-dose PDT significantly improved the distribution of Liporubicin in tumors compared to high-dose PDT (p < 0.05) and ILP alone (p < 0.05). However, both PDT pretreatments did not result in a higher overall drug uptake in tumors or a higher tumor-to-lung drug ratio compared to ILP alone. CONCLUSIONS: Intraoperative low-dose Visudyne-mediated PDT enhances liposomal doxorubicin distribution administered by ILP in sarcomas grown on rodent lungs which is predicted to improve tumor control by ILP.

A novel device for reducing hemolysis provoked by cardiotomy suction during open heart cardiopulmonary bypass surgery: a randomized prospective study.

Since the inception of cardiopulmonary bypass (CPB), little progress has been made concerning the design of cardiotomy suction (CS). Because this is a major source of hemolysis, we decided to test a novel device (Smartsuction [SS]) specifically aimed at minimizing hemolysis during CPB in a clinical setting. Block randomization was carried out on a treated group (SS, n=28) and a control group (CTRL, n=26). Biochemical parameters were taken pre-, peri-, and post CPB and were compared between the two groups using the Student's t-test with statistical significance when P<0.05. No significant differences in patient demographics were observed between the two groups. Lactate dehydrogenase (LDH) and plasma free hemoglobin (PFH) pre-CPB were comparable for the CTRL and SS groups, respectively. LDH peri-CPB was 275+/-100 U/L versus 207+/-83 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 486+/-204 mg/L versus 351+/-176 mg/L for the CTRL and SS groups, respectively (P<0.05). LDH post CPB was 354+/-116 U/L versus 275+/-89 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 549+/-271 mg/L versus 460+/-254 mg/L for the CTRL and SS groups, respectively (P<0.05). Preoperative hematocrit (Hct) of 43+/-5% (CTRL) versus 37+/-5% (SS), and hemoglobin (Hb) of 141+/-16 g/L (CTRL) versus 122+/-17 g/L (SS) were significantly lower in the SS group. However, when normalized (N), the SS was capable of conserving Hct, Hb, and erythrocyte count perioperatively. Erythrocytes (N) were 59+/-5% (CTRL) versus 67+/-9% (SS); Hct (N) was 59+/-6% (CTRL) versus 68+/-9% (SS), and Hb (N) was 61+/-6% (CTRL) versus 70+/-10% (SS) (all P<0.05). This novel SS device evokes significantly lowered blood PFH and LDH values peri- and post CPB compared with the CTRL blood using a CS system. The SS may be a valuable alternative compared to traditional CS techniques.

Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis.

Background. Streptococcus gallolyticus is a causative agent of infective endocarditis associated with colon cancer. Genome sequence of strain UCN34 revealed the existence of 3 pilus loci (pil1, pil2, and pil3). Pili are long filamentous structures playing a key role as adhesive organelles in many pathogens. The pil1 locus encodes 2 LPXTG proteins (Gallo2178 and Gallo2179) and 1 sortase C (Gallo2177). Gallo2179 displaying a functional collagen-binding domain was referred to as the adhesin, whereas Gallo2178 was designated as the major pilin. Methods. S. gallolyticus UCN34, Pil1(+) and Pil1(-), expressing various levels of pil1, and recombinant Lactococcus lactis strains, constitutively expressing pil1, were studied. Polyclonal antibodies raised against the putative pilin subunits Gallo2178 and Gallo2179 were used in immunoblotting and immunogold electron microscopy. The role of pil1 was tested in a rat model of endocarditis. Results. We showed that the pil1 locus (gallo2179-78-77) forms an operon differentially expressed among S. gallolyticus strains. Short pilus appendages were identified both on the surface of S. gallolyticus UCN34 and recombinant L. lactis-expressing pil1. We demonstrated that Pil1 pilus is involved in binding to collagen, biofilm formation, and virulence in experimental endocarditis. Conclusions. This study identifies Pil1 as the first virulence factor characterized in S. gallolyticus.

Increased activation in Broca's area after cognitive remediation in schizophrenia.

Functional magnetic resonance imaging (fMRI) was used to measure changes in cerebral activity in patients with schizophrenia after participation in the Cognitive Remediation Program for Schizophrenia and other related disorders (RECOS). As RECOS therapists make use of problem-solving and verbal mediation techniques, known to be beneficial in the rehabilitation of dysexecutive syndromes, we expected an increased activation of frontal areas after remediation. Executive functioning and cerebral activation during a covert verbal fluency task were measured in eight patients with schizophrenia before (T1) and after (T2) 14 weeks of RECOS therapy. The same measures were recorded in eight patients with schizophrenia who did not participate in RECOS at the same intervals of time (TAU group). Increased activation in Broca's area, as well as improvements in performance of executive/frontal tasks, was observed after cognitive training. Metacognitive techniques of verbalization are hypothesized to be the main factor underlying the brain changes observed in the present study.

The Early Cretaceous San Juan Plutonic Suite, Ecuador: A magma chamber in an oceanic plateau ?

Sections through an oceanic plateau are preserved in tectonic slices in the Western Cordillera of Ecuador (South America). The San Juan section is a sequence of mafic-ultramafic cumulates. To establish that these plutonic rocks formed in an oceanic plateau setting, we have developed criteria that discriminate intrusions of oceanic plateaus from those of other tectonic settings. The mineralogy and crystallization sequence of the cumulates are similar to those of intra-plate magmas. Clinopyroxene predominates throughout, and orthopyroxene is only a minor component. Rocks of intermediate composition are absent, and hornblende is restricted to the uppermost massive gabbros within the sequence. The ultramafic cumulates are very depleted in light rare-earth elements (LREE), whereas the gabbros have flat or slightly enriched LREE patterns. The composition of the basaltic liquid in equilibrium with the peridotite, calculated using olivine compositions and REE contents of clinopyroxene, contains between 16% and 8% MgO and has a flat REE pattern. This melt is geochemically similar to other accreted oceanic plateau basalts, isotropic gabbros, and differentiated sills in western Ecuador. The Ecuadorian intrusive and extrusive rocks have a narrow range of epsilonNd(i) (+8 to +5) and have a rather large range of Pb isotopic ratios. Pb isotope systematics of the San Juan plutonic rocks and mineral separates lie along a mixing line between the depleted mantle (DMM) and the enriched-plume end members. This suggests that the Ecuadorian plutonic rocks generated from the mixing of two mantle sources, a depleted mid-oceanic ridge basalt (MORB) source and an enriched one. The latter is characterized by high (Pb-207/Pb-204)(i) ratios and could reflect a contamination by recycled either lower continental crust or oceanic pelagic sediments and (or) altered oceanic crust (enriched mantle type I, EMI). These data suggest that the San Juan sequence represents the plutonic components of an Early Cretaceous oceanic plateau, which accreted in the Late Cretaceous to the Ecuadorian margin.

Maximal Physiological Parameters during Partial Body-Weight Support Treadmill Testing.

PURPOSE: This study investigated maximal cardiometabolic response while running in a lower body positive pressure treadmill (antigravity treadmill (AG)), which reduces body weight (BW) and impact. The AG is used in rehabilitation of injuries but could have potential for high-speed running, if workload is maximally elevated. METHODS: Fourteen trained (nine male) runners (age 27 ± 5 yr; 10-km personal best, 38.1 ± 1.1 min) completed a treadmill incremental test (CON) to measure aerobic capacity and heart rate (V˙O2max and HRmax). They completed four identical tests (48 h apart, randomized order) on the AG at BW of 100%, 95%, 90%, and 85% (AG100 to AG85). Stride length and rate were measured at peak velocities (Vpeak). RESULTS: V˙O2max (mL·kg·min) was similar across all conditions (men: CON = 66.6 (3.0), AG100 = 65.6 (3.8), AG95 = 65.0 (5.4), AG90 = 65.6 (4.5), and AG85 = 65.0 (4.8); women: CON = 63.0 (4.6), AG100 = 61.4 (4.3), AG95 = 60.7 (4.8), AG90 = 61.4 (3.3), and AG85 = 62.8 (3.9)). Similar results were found for HRmax, except for AG85 in men and AG100 and AG90 in women, which were lower than CON. Vpeak (km·h) in men was 19.7 (0.9) in CON, which was lower than every other condition: AG100 = 21.0 (1.9) (P < 0.05), AG95 = 21.4 (1.8) (P < 0.01), AG90 = 22.3 (2.1) (P < 0.01), and AG85 = 22.6 (1.6) (P < 0.001). In women, Vpeak (km·h) was similar between CON (17.8 (1.1) ) and AG100 (19.3 (1.0)) but higher at AG95 = 19.5 (0.4) (P < 0.05), AG90 = 19.5 (0.8) (P < 0.05), and AG85 = 21.2 (0.9) (P < 0.01). CONCLUSIONS: The AG can be used at maximal exercise intensities at BW of 85% to 95%, reaching faster running speeds than normally feasible. The AG could be used for overspeed running programs at the highest metabolic response levels.

The costs of parasitism and anti-parasitic defense in the common vole

Résumé : Les relations entre un parasite et son hôte sont avant tout marquées par le coût pour l'hôte que représente la ponction de ressources au profit du parasite et ses conséquences sur les traits d'histoires de vie de l'hôte. Pour contenir la réduction de leur valeur reproductive, les hôtes ont acquis au cours de l'évolution des mécanismes soit de lutte contre les parasites, soit de réallocations des ressources. Curieusement les effets des ectoparasites sur la biologie de mammifères ont été peu étudiés. Dans une première expérience à long terme, nous avons examiné sous un angle intégratif si les puces Nosopsyllus fasciatus affectent certains paramètres physiologiques des campagnols des champs Microtus arvalis. Nous avons également testé si les puces peuvent réduire la longévité et si oui, si ce pourrait être dû à une accélération de la sénescence. Ensuite nous avons testé si la simple activation répétée du système immunitaire comme lors d'une infestation chronique pouvait aussi réduire la longévité. Dans une dernière expérience, nous avons d'abord testé si l'infestation par des puces de jeunes campagnols au stade néonatal (21 jours) pouvait modifier leur développement et leur phénotype adulte. Puis nous avons testé si la modification du phénotype adulte est une réponse prédite et potentiellement adaptative pour minimiser les effets des puces à l'âge adulte. Nos résultats montrent que l'infestation par des puces réduit la croissance subadulte, induit une forte anémie et une immunodépression, et augmente le métabolisme de repos. De plus les puces réduisent la longévité et la taille des testicules, réduisant fortement le succès reproducteur potentiel des individus parasités. La taille finale, c'est-à-dire le développement pré-adulte, détermine en grande part la longévité. La réduction de longévité ne devrait pas être due à l'investissement au profit du système immunitaire car l'activation chronique seule du système immunitaire ne réduit pas la longévité. L'infestation néonatale retarde légèrement le développement mais surtout modifie l'hématocrite et réduit les performances locomotrices des campagnols plus de 3 mois après l'infestation. Les effets immédiats du parasitisme sur la physiologie semblent bien supérieurs comparés aux effets à long terme. Nous n'avons pas d'éléments permettant d'affirmer que le parasitisme néonatal prépare les campagnols à faire face aux puces à l'âge adulte. Au contraire, le parasitisme néonatal interagit sur le parasitisme adulte pour augmenter le métabolisme de repos. Cette thèse offre une vision intégrative des mécanismes par lesquels les puces peuvent affecter la valeur reproductive de leurs hôtes. De façon générale, ces résultats 35 montrent l'importance des puces comme force de sélection chez les campagnols. Il est indispensable de prendre en compte les ectoparasites dans l'étude de l'écologie et des dynamiques de populations chez les mammifères. Summary : The relationship between a parasite and its host is fundamentally marked by the costs for host of the withdrawals of resources by parasite and the subsequent reduction in host life-history traits. Hosts have evolved a number of strategies to reduce these costs, either by fighting against the parasite directly or by reallocating resources to reduce costs on lifetime reproductive value. The effects of ectoparasites on burrowing mammals have been scarcely studied. In a first long-term experiment, we examined how fleas Nosopsyllus fasciatus affect physiological levels of the common vole, Microtus arvalis. We also examined whether fleas reduce longevity and if so, if it is due to an early senescence pattern. Then we tested if experimental activation of the immune system by repeated injections of an antigen could result in a shorter longevity. In the last experiment, we tested if short-lasting neonatal parasitism can have long-term effects on phenotype, and if these effects could induce a predictive response to reduce damages when parasitized at the adult stage. We found that parasitism by flea reduced subadult growth, induced anaemia and immunodepression, and increased energy consumption even when resting. Moreover fleas reduce longevity and testes size associated to splenomegaly, suggesting an overall reduction in fitness but we did not find any pattern of accelerated senescence explaining the early death of parasitized voles compared to non-parasitzed. The cost of mounting an immune response throughout life does not impair longevity, suggesting that it is the cost of parasitism that limits the longevity and not the immune investment. Neonatal infestation by fleas has long-term effects on physiology and reduces motor activity more than 3 months after infestation. The modification of physiology due to long-term effects seems weak compared to the immediate effects of adult infestation. We found no evidence that neonatal parasitism prepares voles to mount a predictive adaptive response in order to reduce effects of fleas on fitness components. On the contrary, neonatal parasitism seems to worsen the effect of adult parasitism. This thesis offers an integrative view of mechanisms by which fleas affect their host at the individual level. Overall, our results demonstrate the importance of fleas as a selective force in voles. These results highlight the importance of ectoparasitism in ecology of micromarnrnals and suggest a role in the dynamic of host populations.

L'évangile de Jean et son lecteur

(Résumé de l'ouvrage) La Bible est un texte à lire. Mais qu'est-ce que lire, et comment lire ? Depuis une trentaine d'années, à l'initiative de biblistes tels que Jean Delorme à qui ce livre rend hommage, sont apparues des méthodes de lecture issues de la linguistique : on parle maintenant d'analyse structurale, ou de lecture sémiotique.

Early-onset Crohn's disease is a risk factor for smaller final height.

OBJECTIVES: Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS: Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS: Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION: Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Mechanical external work and recovery at preferred walking speed in obese subjects

PURPOSE: The aim of this study was to compare the mechanical external work (per kg) and pendular energy transduction at preferred walking speed (PWS) in obese versus normal body mass subjects to investigate whether obese adults adopt energy conserving gait mechanics. METHODS: The mechanical external work (Wext) and the fraction of mechanical energy recovered by the pendular mechanism (Rstep) were computed using kinematic data acquired by an optoelectronic system and were compared in 30 obese (OG; body mass index [BMI] = 39.6 +/- 0.6 kg m(-2); 29.5 +/- 1.3 yr) and 19 normal body mass adults (NG; BMI = 21.4 +/- 0.5 kg m(-2); 31.2 +/- 1.2 yr) walking at PWS. RESULTS: PWS was significantly lower in OG (1.18 +/- 0.02 m s(-1)) than in NG (1.33 +/- 0.02 m s(-1); P <or= 0.001). There was no significant difference in Wext per unit mass between groups (OG: 0.36 +/- 0.03 J kg(-1) m(-1); NG: 0.31 +/- 0.02 J kg(-1) m(-1); P = 0.12). Rstep was significantly lower in OG (68.4% +/- 2.0%) compared with NG (74.4% +/- 1.0%; P = 0.01). In OG only, Wext per unit mass was positively correlated with PWS (r = 0.57; P < 0.001). CONCLUSION: Obese adults do not appear to alter their gait to improve pendular energy transduction and may select slower PWS to reduce mechanical and metabolic work.