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F Lebrun

Publications and source records attributed to F Lebrun.

At least 19 recordsLinked to original sources
PubMed2002

Potential role of the membrane in the development of intestinal cellular damage after whole-body gamma irradiation of the rat.

Our study emphasizes the effect of gamma irradiation on intestinal cell membrane fluidity and addresses the potential relationships existing between radiation-induced lipoperoxidation, membrane fluidity, and changes in membrane protein activities. Male Wistar rats were exposed to an 8-Gy total body irradiation (60Co source) and studied 1, 4, and 7 days after irradiation (D1, D4, and D7). Membrane enzyme activities and fluorescence anisotropy were determined on small intestinal crude membrane preparations. The supernatants of membrane preparations as well as plasma were used for malonedialdehyde (MDA) quantification. The effect of carbamylcholine on electrical parameters was estimated on distal ileum placed in Ussing chambers. We observed a decrease in fluorescence anisotropy for at least 7 days, an increase in membrane production of MDA at D4, a decrease in membrane enzyme activities at D4, but an amplification of carbamylcholine-induced increase in short-circuit current at D4 and D7. Furthermore, correlations were observed between the 1,6-diphenyl-1,3,5-hexatriene anisotropy coefficient and sucrase activity and between MDA levels and leucine aminopeptidase activity. Thus, total body irradiation induces changes in intestinal membrane fluidity and an increase in lipoperoxidation. These modifications may have an impact on the activity of membrane proteins involved in intestinal function.

Animals↗
PubMed2002

Alterations of the VIP-stimulated cAMP pathway in rat distal colon after abdominal irradiation.

Ionizing radiation induces hyporesponsiveness of rat colonic mucosa to vasoactive intestinal peptide (VIP). Possible mechanisms responsible for this hyporesponsiveness of the cAMP communication pathway in rat colon were investigated. VIP- and forskolin-stimulated short-circuit current (I(sc)) responses were studied after a 10-Gy abdominal irradiation in Ussing chambers as well as in single, isolated crypts. Adenylyl cyclase (AC) activity and VIP receptor characteristics were determined in mucosal membrane preparations. In addition, alterations in crypt morphology were studied. Impaired secretory responses to VIP and forskolin were observed 4 days after irradiation (decrease of 80%). cAMP analog-stimulated I(sc) responses were unchanged. In isolated crypts, VIP- and forskolin-stimulated cAMP accumulation was markedly reduced by 80 and 50%, respectively. VIP-stimulated AC activity and VIP receptor number were decreased in membrane preparations. No major change of cellularity was associated with these functional alterations. In conclusion, the decreased secretory responses to VIP of rat colon are associated with reduced cAMP accumulation, decreased AC activity, and diminution of VIP receptor numbers without a marked decrease of crypt cell number.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Quantitation of functional mitral regurgitation during bicycle exercise in patients with heart failure.

OBJECTIVES: We sought to examine the feasibility and reliability of quantifying mitral regurgitation (MR) during exercise by Doppler echocardiography in patients with heart failure and to assess the relationship between dynamic MR and systolic pulmonary artery pressure changes. BACKGROUND: The severity of MR can be quantified by using several echocardiographic methods. Quantitation of MR during dynamic exercise has not yet been performed. METHODS: Symptom-limited, semi-supine two-dimensional and Doppler echocardiograms during bicycle exercise were obtained in 27 consecutive patients with heart failure and functional MR. Regurgitant volume was measured at rest and during exercise by the proximal isovelocity surface area (PISA) method and by quantitative Doppler echocardiography. Exercise-induced changes in regurgitant volume were compared with changes in the regurgitant jet area to left atrial area ratio, vena contracta width and trans-tricuspid pressure gradient. RESULTS: The regurgitant volume measured by the PISA method increased from 21 +/- 12 ml (range 5 to 55) at rest to 39 +/- 23 ml (range 8 to 85) during exercise (p < 0.0001). The difference between two observers was low for both rest (2.0 +/- 2.7 ml) and exercise measurements (3.5 +/- 6.2 ml). The regurgitant volume measured by quantitative Doppler echocardiography increased from 29 +/- 13 to 49 +/- 24 ml (p = 0.0001). Excellent correlation between the two methods was obtained with exercise (r = 0.92). Exercise-induced changes in regurgitant volume, as measured by the PISA method, correlated well with regurgitant volume changes measured by quantitative Doppler echocardiography (r = 0.88), changes in vena contracta width (r = 0.82) and changes in trans-tricuspid pressure gradient (r = 0.73), but not with changes in regurgitant jet area to left atrial area ratio (r = 0.29). Seventeen patients stopped exercise because of fatigue and 10 because of dyspnea. These 10 patients exhibited greater increases in regurgitant volume (34 +/- 6 vs. 11 +/- 8 ml), corresponding to a significant elevation of the trans-tricuspid gradient (48 +/- 14 vs. 20 +/- 14 mm Hg). CONCLUSIONS: Quantitation of functional MR during exercise is feasible in patients with heart failure. There is a good correlation between regurgitant volume measured during exercise by the PISA method and that obtained by quantitative Doppler echocardiography, suggesting that the technique is reliable. An increase in mitral regurgitant volume during dynamic exercise correlates well with elevation of systolic pulmonary artery pressure.

Bicycling↗
PubMed2001

[Pneumomediastinum in children].

Pneumomediastinum in children is diagnosed in two circumstances: cervical subcutaneous emphysema or radiological findings. The predominant symptoms are dyspnoea, stabbing chest pain, sore throat and dysphagia. Traumatic injuries and pulmonary diseases such as asthma are the most common causes of pneumomediastinum. It may rarely result from iatrogenic manoeuvres or acidocetosis. Spontaneous mediastinal emphysema is seldom reported in children. Chest X-ray films are essential investigations. The treatment is directed towards the underlying cause, with conservative management being sufficient in most cases. However, the risk of surveying of pneumothorax or tension pneumomediastinum justifies close clinical follow-up in a specialised care unit. The onset of these pathologies necessitates a more aggressive therapy by aspiration through percutaneous catheter placed in the mediastinum.

Asthma↗
PubMed2000

The effect of cysteine and 2,4-dinitrophenol on heme and nonheme absorption in a rat intestinal model.

Previous studies have showed that purified heme iron forms insoluble polymers that are poorly absorbed. The presence of peptides and of amino acids maintaining heme iron in a soluble form could improve its bioavailability. The digestive uptake and transfer of a concentrated hydrolysate of heme peptides (HPH) and of iron gluconate (Gluc) at 100 µM were compared in vitro in a Ussing chamber. The effects of an enhancing amino acid (L-cysteine) on the uptake and transfer of both forms were assessed. An inhibitor of the oxidative phosphorylation (2,4-dinitrophenol; DNP) was used to differentiate the active and passive mechanisms of the absorption. The mucosal uptake (%Tot) and enterocyte transfer (%S) of the two sources of iron did not differ. DNP significantly reduced %Tot and %S of both forms. Cysteine significantly enhanced %Tot and %S of HPH and Gluc, partly corrected the inhibition exerted by DNP on %Tot of HPH and %S of both forms, and fully restored %Tot of Gluc. In presence of peptides produced by globin hydrolysis, the absorption of hemoglobin iron was efficient; it was mostly energy dependent and, therefore, should have occurred by a regulated transcellular pathway. Cysteine enhanced the passive uptake of iron and the passive processes involved in the enterocyte transfer of the common pool made of both sources (heme and nonheme) of iron. These results showed that heme iron can be purified and concentrated without impairing its digestive absorption, provided it remains in presence of peptides or amino acids.

Journal Article↗
PubMed2000

Radiation induced cytochrome c release causes loss of rat colonic fluid absorption by damage to crypts and pericryptal myofibroblasts.

BACKGROUND: Therapeutic or accidental exposure to radiation commonly causes gastrointestinal disturbances, including diarrhoea. Rats subjected to whole body ionising radiation at a dose of 8 Gy lose their capacity to absorb fluid via the descending colon after four days. After seven days, fluid absorption recovers to control levels. AIMS: To investigate the effect of ionising radiation on colonic permeability together with its effect on mitochondria dependent apoptotic signals and intercellular adhesion molecules. METHODS: Rats were irradiated with doses of 0-12 Gy. Colonic permeability was measured by accumulation of fluorescein isothiocyanate (FITC) dextran in crypt lumens. Changes in levels of cytochrome c, caspase 3, E and OB cadherin, beta-catenin smooth muscle actin, and collagen IV were assessed using immunocytochemistry with confocal microscopy. RESULTS: Cytosolic cytochrome c increased after 8 Gy (t(1/2) 1.4 (0.6) hours) and peaked at approximately six hours. Caspase 3 increased more slowly, particularly in crypt epithelial cells (t(1/2) 57 (14.5) hours). Pericryptal myofibroblasts disintegrated within 24 hours as was evident from loss of OB cadherin and smooth muscle actin. This coincided with increased crypt permeability to dextran. Intercellular adhesion between crypt luminal cells was not lost until day 4 when both beta-catenin and E-cadherin were minimal. The half maximal dose-response for these effects was in the range 2-4 Gy. Recovery of colonic transport was concurrent with recovery of pericryptal smooth muscle actin and OB cadherin. The pan caspase inhibitor Z-Val-Ala-Asp.fluoromethylketone (1 mg/kg per day) had a small effect in conserving the pericryptal sheath myofibroblasts and sheath permeability but had no systemic therapeutic effects. CONCLUSIONS: These data suggest that radiation damage to the colon may be initiated by mitochondrial events. Loss of crypt fluid absorption and increased permeability coincided with decreased intercellular adhesion between crypt epithelial cells and loss of pericryptal sheath barrier function.

Animals↗
PubMed1999

Neurological and physical maturation in normal growth singletons from 37 to 41 weeks' gestation.

An evaluator blinded to gestational age (GA) assessed a cohort of 397 singletons born at between 37 and 41 week's gestation, by looking at 11 criteria exploring neurological maturity and 12 criteria exploring physical maturity. The analysis of correlation coefficients shows various degrees of association between GA and each of the criteria examined. A highly significant correlation (p < 0.001) was found for 4 neurological criteria defining passive tone in limbs and sucking reflex. The activity of flexor muscles of the neck and crossed extension reflex were also associated with maturity but weakly (p < 0.01). A highly significant correlation (p < 0.001) was found for 8 of the physical criteria, skin colour and texture, lanugo, ear firmness, genitalia, breast size, nipple formation and plantar skin creases. Oedema, skull firmness and ear form were also associated but weakly. With multivariate analysis combining the neurological and physical criteria, predictive values ranked in the following order: 1) plantar skin, 2) breast size, 3) sucking reflex, 4) scarf sign, 5) skin colour, 6) genitalia, 7) popliteal angle, 8) return to flexion of forearms, 9) dorsiflexion angle. In conclusion, a score based on physical and neurological criteria is associated with duration of pregnancy (r2 = 0.32) between 37 and 41 weeks' gestation. Such an instrument allows us to study fetal maturity as a variable independent of GA, and therefore makes it possible to identify various influences that may modify maturational rate during the last weeks of pregnancy.

Cohort Studies↗
PubMed1999

Modified absorptive and secretory processes in the rat distal colon after neutron irradiation: in vivo and in vitro studies.

Impaired fluid and electrolyte transport in the intestine is a well-recognized characteristic of radiation-induced pathologies in the gastrointestinal tract. The aim of this study was to investigate the responsiveness of the epithelium of the colon of the rat to electrical and pharmacological (serotonin, carbachol) stimulation concomitantly with in vivo assessment of the absorptive capacity of the colon at 1, 3, 5 and 7 days after 3.8 Gy whole-body exposure to neutrons. The responsiveness of rat colon in vitro to electrical stimulation and the number of mast cells were measured to examine the role of neuroimmune networks in radiation-induced dysfunction. Animals showed an impaired capacity of the colon to absorb water and sodium from 3 to 5 days after irradiation together with decreased responsiveness to electrical and pharmacological stimulation. The time course of decreased responsiveness to neural stimulation was similar to that of impaired absorption observed in vivo, but it was not correlated with variations in mast cell numbers. Histological (mast cells) and biochemical analyses (myeloperoxidase and NO synthase activities) did not find evidence of a marked infiltration and/or activation of inflammatory cells. Thus the impaired absorptive capacity of the colon observed after irradiation occurs concomitantly with decreased neural influence, and is possibly related to reduced epithelial functional capacity but not to decreased mast cell numbers.

Animals↗
PubMed1998

Ionizing radiation stimulates muscarinic regulation of rat intestinal mucosal function.

The aim of this study was to determine whether ionizing radiation modifies muscarinic regulation of intestinal mucosal function. Rats exposed to total body 8-Gy gamma-irradiation or sham irradiated were studied up to 21 days after irradiation. Basal and carbachol-stimulated short-circuit current (Isc) and transepithelial conductance (Gt) of stripped ileum were determined in Ussing chambers. Muscarinic receptor characteristics using the muscarinic antagonist [3H]quinuclidinyl benzilate and three unlabeled antagonists were measured in small intestinal plasma membranes together with two marker enzyme activities (sucrase, Na+-K+-ATPase). Enzyme activities were decreased 4 days after irradiation (day 4). Basal electrical parameters were unchanged. Maximal carbachol-induced changes in Isc and Gt were increased at day 4 (maximal DeltaIsc = 195.8 +/- 14.7 microA/cm2, n = 19, vs. 115.4 +/- 8.2 microA/cm2, n = 63, for control rats) and unchanged at day 7. Dissociation constant was decreased at day 4 (0.73 +/- 0.29 nM, n = 10, vs. 2.14 +/- 0.39 nM, n = 13, for control rats) but unchanged at day 7, without change in binding site number. Thus total body irradiation induces a temporary stimulation of cholinergic regulation of mucosal intestinal function that may result in radiation-induced diarrhea.

Animals↗
PubMed1996

Exposure to either gamma or a mixed neutron/gamma field irradiation modifies vasoactive intestinal peptide receptor characteristics in membranes isolated from pig jejunum.

The effect of acute whole body exposure to ionizing radiation was investigated on intestinal vasoactive intestinal peptide (VIP) receptors and adenylate cyclase activity in membranes isolated from pig jejunum. Pigs under light anaesthesia were exposed to a single dose (6 Gy) of gamma (gamma) or to mixed neutron/gamma field (ratio 1:1; neutron/gamma) irradiation. Seven days after irradiation, plasma-membranes were prepared from post mortem jejunal mucosal scrapings. Marker enzyme activities (sucrase, leucine aminopeptidase (LAP), Na,K-ATPase) were measured in each preparation. The characteristics (KD, Bmax) of VIP receptors were determined using 125I-labelled VIP. In addition VIP-sensitive adenylate cyclase activity was measured. Results showed that enzyme activities were reduced following both gamma (sucrase 67%; LAP 53%; Na/K-ATPase 29%; N = 7) and neutron/gamma (sucrase 53%; LAP 59%; Na/K-ATPase 68%; N = 5) compared with control values (N = 5). VIP receptor affinity was decreased following either type of irradiation (gamma or neutron/gamma P < 0.01) and receptor numbers increased. Both VIP- and forskolin-stimulated adenylate cyclase activities were reduced but the sensitivity of the enzyme remained the same for VIP (EC50 values (nmol dm-3)-control-1.27 +/- 0.35; gamma-2.18 +/- 0.41; neutron/gamma-1.91 +/- 0.28). In conclusion, exposure to either gamma or neutron/gamma irradiation attenuates intestinal enzyme activities and VIP receptor affinity but increases VIP receptor numbers.

Adenylyl Cyclases↗
PubMed1995

The parietal sheet of Bowman's capsule of rat renal glomerulus: a target of endothelin and PAF.

On the basis of intracellular calcium concentration ([Ca2+]i) measurements, we have previously reported that the parietal sheet of Bowman's capsule was sensitive to cholinergic agonists. The aim of the present work was to investigate whether this structure could be also a target of endothelin and platelet-activating factor (PAF), since we observed [Ca2+]i increases in response to both agonists in the glomerulus, but which were very different from that induced by carbachol. For this purpose, we measured [Ca2+]i on single microdissected parietal sheets, using a fura 2 microfluorescence technique and compared the effects of maximal concentrations of the three agonists (10(-7), 10(-8), and 10(-4) M for endothelin, PAF, and carbachol, respectively) under various experimental conditions. We observed that, like in the glomerulus, endothelin and PAF induced, in the parietal sheet, [Ca2+]i responses that differed in many respects from those found with carbachol. Thus, in the presence of 2 mM external calcium, 1) endothelin and PAF responses spontaneously declined to basal level, whereas a stationary plateau was observed after a sharp peak of [Ca2+]i with carbachol; 2) the magnitude of [Ca2+]i peak was smaller with endothelin and PAF than with carbachol; and 3) endothelin and PAF, but not carbachol, induced a homologous dose-dependent desensitization. Moreover, in the absence of external calcium, endothelin and PAF responses were smaller than carbachol response, although all three responses apparently resulted from release of calcium ions from the same internal pool. In additional experiments, we observed that, like carbachol, endothelin and PAF contracted the parietal sheet, which is only composed of myoepithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Kainate-induced status epilepticus leads to a delayed increase in various specific glutamate metabotropic receptor responses in the hippocampus.

Neuronal loss and gliosis were detected in the rat hippocampus soon after unilateral intra-amygdala injection of kainate (KA) (2.5 nmol) while solid mossy fiber sprouting could be seen only fourteen days after this injection. Using this experimental model, we examined the metabotropic glutamate receptor (mGluR)-induced inositol phosphate (IP) formation in hippocampal synaptoneurosomes and slices. In synaptoneurosomes prepared from ipsilateral hippocampi fourteen days following injection, there were no significant changes in mGluR- and carbachol(CARB)-stimulated IPs syntheses when sham-operated and KA-injected animals were compared. In the corresponding hippocampal slices, significant increases of the mGluR responses mediated by ibotenate (IBO) and aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD) were noted after KA application. The net stimulation values respectively expressed in a pair-wise fashion for buffer-injected control and KA-treated animals were IBO: 1,947 +/- 457 and 10,553 +/- 1,242; t-ACPD: 1,557 +/- 662 and 9,449 +/- 2,251 dpm/mg protein respectively. Significantly augmented mGluR responses in hippocampal slices were also measured at 7, 42 and 92 days after KA injection. There were, however, no significant increases in CARB-stimulated phosphoinositide hydrolysis in the hippocampal slices at all time-intervals after KA administration. These findings show that there are differences between the mGluR responses in hippocampal synaptoneurosome and slice preparations, suggesting the presence of two distinct populations of mGluR in each of these two models. The large specific increases in certain mGluR activities after KA-induced status epilepticus in hippocampal slices could represent one of the molecular mechanisms which underlie the profound morphological changes, in particular gliosis or mossy fiber sprouting, which follow the KA-induced status epilepticus.

Animals↗
PubMed1994

Ontogenesis of quisqualate-associated phosphoinositide metabolism in various regions of the rat nervous system.

The effect of postnatal age on phosphoinositide metabolism per se and on quisqualate-stimulated phosphoinositide metabolism was characterized in synaptoneurosomes prepared from nine different regions of the rat nervous system, namely the brainstem, cerebellum, cerebral cortex, colliculi, hippocampus, hypothalamus, olfactory bulb, spinal cord and striatum. In the hippocampus, striatum, cerebellum, cerebral cortex, brainstem, colliculus and spinal cord, the basal levels of inositol phosphate (inositol-1-phosphate+inositol-4,5-bisphosphate) formation were maximal two days after birth and declined steeply to steady-state levels from the age of 10 postnatal days. Similarly, in the olfactory bulb, basal inositol phosphate synthesis did not significantly change when measured during the period from postnatal day 10 to 42. The extent of [3H]-inositol labelling of phosphoinositides as a function of age presented similar profiles when measured in hippocampal, striatal, cerebellar and cerebral cortical synaptoneurosomes, i.e. maximal at perinatal ages and minimal at adult ages. In the hypothalamus, [3H]-inositol labelling of phosphoinositides showed an increase from postnatal day 12 to higher levels from postnatal days 14 to 18 subsequently followed by a dramatic increase from postnatal day 21 to 42. A similar developmental trend was also obtained for basal inositol phosphate synthesis. On the whole, four types of developmental profiles for quisqualate-stimulated inositol phosphate formation (expressed as the percentage of the basal level and as the difference between stimulated and basal levels of radioactive inositol phosphates) were obtained depending on the nervous system region studied. In the early, prenatally developed nervous system regions, namely the brainstem and the spinal cord, no postnatal stimulation peaks of quisqualate-induced inositol phosphate formation were recorded. This was also the case for the colliculi when the stimulation of IP formation was expressed as the difference in basal and stimulated levels of inositol phosphates. Secondly, in the olfactory bulb a region known to possess a continuous capacity for developmental plasticity both structurally and functionally during the first three weeks of postnatal development, a simultaneous sustained high level of quisqualate stimulation of phosphoinositide metabolism (fluctuating around 200% of the basal level) during the early postnatal period was evident. Thirdly, in regions of the central nervous system like the cerebellum, cerebral cortex, hippocampus and the striatum known to undergo intense developmental activity during the first two postnatal weeks, peaks of quisqualate-stimulated phosphoinositide metabolism were initially detected around the first week after birth in each of these brain areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗