Biomedical subjects

P Poulain

Publications and source records attributed to P Poulain.

At least 19 recordsLinked to original sources

PubMed2006

Performances of Wang-Landau algorithms for continuous systems.

The relative performances of different implementations of the Wang-Landau method are assessed on two classes of systems with continuous degrees of freedom, namely, two polypeptides and two atomic Lennard-Jones clusters. Parallel tempering Monte Carlo simulations serve as a reference, and we pay particular attention to the variations of the multiplicative factor f during the course of the simulation. For the systems studied, the Wang-Landau method is found to be of comparable accuracy as parallel tempering, but has significant difficulties in reproducing low-temperature transitions exhibited by the Lennard-Jones clusters at low temperature. Using a complementary order parameter and calculating a two-dimensional joint density of states significantly improves the situation, especially for the notoriously difficult LJ(38) system. However, while parallel tempering easily converges for LJ(31), we have not been able to get data of comparable accuracy with Wang-Landau multicanonical sampling.

Journal Article↗

PubMed2006

Comparison of the fragmentation pattern induced by collisions, laser excitation and electron capture. Influence of the initial excitation.

Collision-induced dissociation, laser-induced dissociation and electron-capture dissociation are compared on a singly and doubly protonated pentapeptide. The dissociation spectrum depends on the excitation mechanism and on the charge state of the peptide. The comparison of these results with the conformations obtained from Monte Carlo simulations suggests that the de-excitation mechanism following a laser or an electron-capture excitation is related to the initial geometry of the peptide.

Computer Simulation↗

PubMed2006

[Prenatal diagnosis of sirenomelia].

Sirenomelia sequence associates a fusion of inferior legs with renal anomalies until bilateral agenesis. It is a rare and lethal polymalformation. The purpose of the ultrasonographic study is to identify the sirenomelia as early as possible during pregnancy and to differentiate it from caudal regression syndrome. A case of sirenomelia diagnosed early is reported together with a review of the literature. The ultrasonographic diagnosis, associated defects, the interest of color Doppler study of abdominal vasculature are discussed. Antenatal ultrasonographic diagnosis should be obtained as early as possible, before 20th gestational week at the latest. Color Doppler is helpful to confirm the diagnosis in case of bilateral renal agenesis. The main differences between sirenomelia and caudal regression syndrome (which requires a very different genetic counselling) are summarized in a table.

Abdomen↗

PubMed2005

Size distribution of fat globules in human colostrum, breast milk, and infant formula.

Only a few results are available on the size of human milk fat globules (MFG), despite its significance regarding fat digestion in the infant, and no data are available at <24 h postpartum (PP). We measured the MFG size distribution in colostrum and transitional human milk in comparison with fat globules of mature milk and infant formula. Colostrum and transitional milk samples from 18 mothers were collected regularly during 4 d PP and compared with mature milk samples of 17 different mothers and 4 infant formulas. The size distribution was measured by laser light scattering. For further characterization, the zeta-potential of some mature MFG was measured by laser Doppler electrophoresis. The MFG diameter decreased sigmoidally in the first days. At <12 h PP, the mode diameter was 8.9 +/- 1.0 microm vs 2.8 +/-0.3 microm at 96 h PP. Thus, the surface area of MFG increased from 1.1 +/-0.3 to 5.4 +/-0.7 m2/g between colostrum and transitional milk. In mature milk, the MFG diameter was 4 microm on average and increased with advancing lactation, whereas the droplets in infant formula measured 0.4 microm. The zeta potential of mature MFG was -7.8 +/- 0.1 mV. The fat globules are larger in early colostrum than in transitional and mature human milk and in contrast with the small-sized fat droplets in infant formula. Human MFG also have a low negative surface charge compared with bovine globules. These structural differences can be of nutritional significance for the infant.

Adult↗

PubMed2003

[Antenatal metastatic neuroblastoma: prognostic criteria. A case report].

Neuroblastoma, the most common malignant tumor in the neonatal period is metastatic in 25 to 50% of cases. While the prognosis of antenatal neuroblastoma is often considered as favorable, included in the most common metastatic stage (Stage IV S), it can lead to fetal or neonatal death. We report a case of a fetus with a stage IV neuroblastoma who died in utero. The most important prognostic factor is tumor stage, making sonographic detection of metastasis essential. Nevertheless, accurate staging remains difficult by sonography. When metastatic neuroblastoma is suspected, sonographic survey has to be reinforced, and if serious criteria such as massive hepatomegaly, placentomegally or hydrops appear, delivery must be considered.

Adrenal Gland Neoplasms↗

PubMed2002

Levetiracetam opposes the action of GABAA antagonists in hypothalamic neurones.

Whole-cell current-clamp recordings in guinea-pig brain slices were used to assess the effect of the novel antiepileptic drug levetiracetam (LEV; Keppra) on the gamma-aminobutyric acid-A (GABA(A)) responses evoked by exogenous applications of the agonists GABA and muscimol on hypothalamic neurones. LEV (40 microM) had no direct effect on GABA(A) responses but it occluded the GABA(A)-receptor blocking action of bicuculline-methiodide (100 microM) and, to a lesser extent, the GABA(A)-receptor blocking action of gabazine (50 microM). While previous reports have indicated that the inhibition by LEV of the epileptiform hyperexcitability induced by bicuculline in rat hippocampus might occur via non-GABAergic mechanisms, the present data suggest a possible indirect modulation by LEV of GABA-gated currents in guinea-pig hypothalamic neurones.

Action Potentials↗

PubMed2002

[Factors associated with the choice of breast or bottle-feeding for hospitalized newborns].

UNLABELLED: This study was carried out in Rennes's maternity hospitals (France), to determine the breastfeeding rate for newborns hospitalized after birth, as well as the factors associated with the choice to breastfeed or not in these conditions. METHODS: Three hundred and twenty mothers delivered in Rennes Teaching Hospital, whose neonates were transferred in neonatal care unit, were questioned about their choice for neonate feeding. RESULTS: Three hundred and eight of the 320 mothers concerned by the study answered our interview. Fifty one percent of them chose to breast feed, which is near the breastfeeding rate of the general population of Rennes' maternity hospitals (52%). A high sociocultural level, a mother previously breastfed herself, and a previous breast feeding (RR = 5.2; P < 10(-8)) were associated with the choice of breastfeeding. Factors concerning the information of the mothers were also associated with the choice of breastfeeding information during the preparation to birth sessions (RR = 1.7; P < 10(-5)), individual information on the breastfeeding of an ill newborn (RR = 1.5; P < 0.01), and the simple advice to breastfeed given by a health care professional (RR = 2; P < 10(-8)). Of the four qualities named, the more breast-milk qualities a mother knew, the higher breastfeeding rate was (10% for none, 27% for one, 54% for two, and 76% for three or four). Concerning the postnatal factors, gestational age below 31 weeks multiplied breast feeding by 1.5 (P < 0.05), and an early contact mother-child (first day) by 1.3 (P < 0.05). CONCLUSION: This study pointed out the populations at risk of no breastfeeding. Informations on the properties of breastfeeding given to mothers by health care professionals may influence them in their choice of breast feeding or not their ill newborn.

Adult↗

PubMed2002

[Markers of infection and inflammation in the amniotic fluid: therapeutic contribution of amniocentesis].

A part of preterm labor with intact membranes seems to be related to amniotic infection or local inflammatory process. In these cases, amniotic fluid is collected by amniocentesis for bacteriological studies: amniotic cultures are positive in 10% and polymerase chain reaction (PCR) in 40-50%. Interleukin 6 (IL6) concentrations are elevated in cases with amniotic infection and in some cases with negative cultures. IL6 amniotic concentrations are predictive of premature delivery and neonatal morbidity. Matrix metalloproteinases (MMP) are endogenous enzymes implicated in membrane weakening. Amniotic concentrations of these enzymes seem to be predictive of premature delivery and neonatal prognosis. Furthermore, at the time of genetic amniocentesis, IL6 and MMP concentrations are markers for preterm delivery. In the second half of gestation, amniocentesis is a safe procedure complicated in less than 1% of cases, although specific evaluation in cases of premature labor is missing. Nevertheless, as long as there is no evidence of any benefit in this procedure, there is no indication for amniocentesis in premature labor with intact membranes in general practice.

Amniocentesis↗

PubMed2001

Morphine and alternative opioids in cancer pain: the EAPC recommendations.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Administration, Oral↗

PubMed2001

Noradrenaline modulates GABA-mediated synaptic transmission in neurones of the mediolateral part of the guinea pig lateral septum via local circuits.

The response to bath-applied noradrenaline (NA, 50 microM) was tested with conventional intracellular recordings in neurones of the mediolateral part of the lateral septum (LSml) by using guinea-pig brain slices. NA elicited direct hyperpolarizations and depolarizations and affected the frequency of tetrodotoxin (TTX)- and bicuculline-sensitive inhibitory post-synaptic potentials (IPSPs). Decrease or increase in IPSPs frequency was observed in 37.6 and 18.2% neurones respectively. Frequency of bicuculline-sensitive miniature IPSPs recorded under TTX was unchanged. Increase in IPSPs frequency was blocked by TTX and was observed during iontophoretic application of NA in the LSml. Taken together, these data suggest that NA hyperpolarizes or depolarizes local presynaptic GABAergic neurones to cause alterations in action potential-dependent transmitter release. NA-induced decrease or increase in IPSPs frequency were respectively mimicked by clonidine and L-phenylephrine and blocked by yohimbine and prazosin, indicating that NA modifies release of GABA by activation of alpha(2) and alpha(1) adrenoceptors at the somato-dendritic region of presynaptic GABAergic neurones. These findings show that, in addition to their direct input from NA afferents, LSml neurones receive a indirect input by way of GABAergic interneurones. These interneurones may serve as inhibitory relays for noradrenergic afferents originating from the locus coeruleus and may be involved in the NA control of LSml functions.

Adrenergic alpha-Agonists↗

PubMed2001

[Thymoma and disseminated lupus erythematosus. Two new cases and review of the literature].

INTRODUCTION: Thymoma is a tumour originating in the epithelial cells of the thymus, associated with several immunologic disorders. The association of thymoma with systemic lupus erythematosus has rarely been described. We report two cases of this association. EXEGESIS: Description of two cases and a review of the literature. Mr T. was 41 years old when the diagnosis of thymoma and lupus was made. The thymectomy did not influence the evolution of his lupus. Mrs G. had been treated because of a lupus for 8 years prior to developing a thymoma. One year later she presented with erythroblastopenia, which was only sensitive to cyclosporin. CONCLUSION: The association between lupus and thymoma has been reported in 36 cases in the literature. Thymoma is benign in 59% of the cases. The clinical presentation of lupus is nonspecific except for age, median 48 years, and sex ratio, 4:3. The clinical outcome of the lupus is not influenced by the thymectomy. Thymoma may precede lupus with a delay of several years or it may be diagnosed concurrently or several years later. This association is not accidental, though the pathogenic link between these conditions remains unknown. One could suppose that the decrease of the thymic function in the course of thymoma could enhance the expression of autoreactive T lymphocytes as well as the activation of B cells. Patients should be followed after thymectomy because autoimmune diseases, particularly lupus, may develop belatedly. On the other hand, thymoma may be suspected mainly when lupus occurs in patients around 50 years of age.

Adult↗

PubMed2001

Two distinct types of repetitive bursting activity mediated by NMDA in hypothalamic neurons in vitro.

Hypothalamic magnocellular dorsal nucleus neurons were recorded from adult guinea pig brain slices with the whole-cell patch-clamp technique to determine the effects of N-methyl-D-aspartate (NMDA) applied in the bath or by iontophoresis. In a majority of cells (59 of 77, 76.6%), rhythmic bursting discharges were evoked by specific activation of NMDA receptors when the membrane was more negative than -60 mV. This endogenous rhythmic activity was resistant to tetrodotoxin. It was suppressed by removal of extracellular Mg2+, indicating the involvement of the voltage-dependent block of the NMDA channel by Mg2+. Application of thapsigargin showed that rhythmic activity did not depend on the release of Ca2+ from reticulum stores. Blockers of Ca2+ conductances Ni2+ and nifedipine had no effects on the bursts. Their repolarization did not involve the activation of a strophantidin- or ouabain-sensitive pump, but partly depended on an apamine-sensitive Ca2+-dependent K+current. In a small subset of cells (9 of 69, 13%), specific activation of NMDA receptors induced another type of bursting activity which consisted of repetitive low-threshold spikes sustaining bursts of action potentials. Rhythmic low-threshold spikes subsisted in the presence of tetrodotoxin but were suppressed by Ni2+. Increasing the amount of NMDA brought about a switch from the rhythmic low-threshold spike burst firing to the rhythmic bursting activity observed for the majority of cells. The present data show for the first time that NMDA receptor activation can induce two independent rhythmic bursting behaviours in the same neuron, probably depending on the strength of the glutamatergic drive.

Action Potentials↗

PubMed2001

Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.

Statins are inhibitors of the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In addition to reducing LDL cholesterol, statin treatment increases the levels of the antiatherogenic HDL and its major apolipoprotein apoA-I. Here, we investigated the molecular mechanisms of apoA-I regulation by statins. Treatment with statins increased apoA-I mRNA levels in human HepG2 hepatoma cells, and this effect was reversed by the addition of mevalonate, implicating HMG-CoA reductase as the relevant target of these drugs. Pretreatment with Actinomycin D abolished the increase of apoA-I mRNA, indicating that statins act at the transcriptional level. Indeed, statins increased the human apoA-I promoter activity in transfected cells, and we have identified a statin response element that coincides with a PPARalpha response element known to confer fibrate responsiveness to this gene. The statin effect could be abolished not only by mevalonate, but also by geranylgeranyl pyrophosphate, whereas inhibition of geranylgeranyl transferase activity or treatment with an inhibitor of the Rho GTP-binding protein family increased PPARalpha activity. Using dominant negative forms of these proteins, we found that Rho A itself mediates this response. Because cotreatment with statins and fibrates activated PPARalpha in a synergistic manner, these observations provide a molecular basis for combination treatment with statins and fibrates in coronary heart disease.

Animals↗

PubMed2001

PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance.

Peroxisome proliferator-activated receptor (PPAR)-alpha controls the expression of genes involved in lipid metabolism. PPAR-alpha furthermore participates to maintain blood glucose during acute metabolic stress, as shown in PPAR-alpha-null mice, which develop severe hypoglycemia when fasted. Here, we assessed a potential role for PPAR-alpha in glucose homeostasis in response to long-term high-fat feeding. When subjected to this nutritional challenge, PPAR-alpha-null mice remained normoglycemic and normoinsulinemic, whereas wild-type mice became hyperinsulinemic (190%; P < 0.05) and slightly hyperglycemic (120%; NS). Insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) were performed to evaluate insulin resistance (IR). Under standard diet, the response to both tests was similar in wild-type and PPAR-alpha-null mice. Under high-fat diet, however, the efficiency of insulin in ITT was reduced and the amount of hyperglycemia in GTT was increased only in wild-type and not in PPAR-alpha-null mice. The IR index, calculated as the product of the areas under glucose and insulin curves in GTT, increased fourfold in high-fat-fed wild-type mice, whereas it remained unchanged in PPAR-alpha-null mice. In contrast, PPAR-alpha deficiency allowed the twofold rise in adiposity and blood leptin levels elicited by the diet. Thus, the absence of PPAR-alpha dissociates IR from high-fat diet-induced increase in adiposity. The effects of PPAR-alpha deficiency on glucose homeostasis seem not to occur via the pancreas, because glucose-stimulated insulin secretion of islets was not influenced by the PPAR-alpha genotype. These data suggest that PPAR-alpha plays a role for the development of IR in response to a Western-type high-fat diet.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Cortical control of somato-cardiovascular integration: neuroanatomical studies.

This paper will discuss experiments dedicated to the exploration of pathways linking the sensorimotor cortex (SMC) and the main bulbar nuclei involved in cardiovascular control: the nucleus tractus solitarius (NTS), the dorsal nucleus of the vagus (DMV) and the rostral ventrolateral medulla (RVLM). Results obtained through neurofunctional and neuroanatomical methods are presented in order to bring new answers to relevant points concerning somato-cardiovascular integration: firstly to show the ability of the SMC to influence neurons in bulbar cardiovascular nuclei, and secondly to identify pathways that transmit such influences. The neurofunctional approach, based on the identification of Fos-like immunoreactive neurons, indicated that the SMC has functional connections with cardiovascular bulbar nuclei. The neuroanatomical approach, which employed retrograde and anterograde axonal tracing methods, provided evidence of direct projections from the SMC to NTS/DMV and RVLM. Furthermore, experiments showed clearly that corticospinal neurons sent collaterals to bulbar cardiovascular nuclei, especially to the RVLM. Direct cortical projections to the NTS/DMV and the RVLM provide the anatomical basis for cortical influences on the baroreceptor reflex and sympathetic vasomotor mechanisms for blood pressure control, and support the hypothesis of cortical commands coupling somatic and cardiovascular outputs for action.

Animals↗

PubMed2000

Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity.

Fibrates and glitazones are two classes of drugs currently used in the treatment of dyslipidemia and insulin resistance (IR), respectively. Whereas glitazones are insulin sensitizers acting via activation of the peroxisome proliferator-activated receptor (PPAR) gamma subtype, fibrates exert their lipid-lowering activity via PPARalpha. To determine whether PPARalpha activators also improve insulin sensitivity, we measured the capacity of three PPARalpha-selective agonists, fenofibrate, ciprofibrate, and the new compound GW9578, in two rodent models of high fat diet-induced (C57BL/6 mice) or genetic (obese Zucker rats) IR. At doses yielding serum concentrations shown to activate selectively PPARalpha, these compounds markedly lowered hyperinsulinemia and, when present, hyperglycemia in both animal models. This effect relied on the improvement of insulin action on glucose utilization, as indicated by a lower insulin peak in response to intraperitoneal glucose in ciprofibrate-treated IR obese Zucker rats. In addition, fenofibrate treatment prevented high fat diet-induced increase of body weight and adipose tissue mass without influencing caloric intake. The specificity for PPARalpha activation in vivo was demonstrated by marked alterations in the expression of PPARalpha target genes, whereas PPARgamma target gene mRNA levels did not change in treated animals. These results indicate that compounds with a selective PPARalpha activation profile reduce insulin resistance without having adverse effects on body weight and adipose tissue mass in animal models of IR.

Adipose Tissue↗

PubMed2000

CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors.

BACKGROUND: The scavenger receptors are cell-surface receptors for native and modified lipoproteins that play a critical role in the accumulation of lipids by macrophages. CLA-1/SR-BI binds HDL with high affinity and is involved in the cholesterol reverse-transport pathway. Peroxisome proliferator-activated receptors (PPARs) are transcription factors regulating the expression of genes implicated in lipid metabolism, cellular differentiation, and inflammation. Here, we investigated the expression of CLA-1/SR-BI in macrophages and its regulation by PPARs. METHODS AND RESULTS: CLA-1 is undetectable in human monocytes and is induced upon differentiation into macrophages. Immunohistological analysis on human atherosclerotic lesions showed high expression of CLA-1 in macrophages of the lipid core colocalizing with PPARalpha and PPARgamma staining. Activation of PPARalpha and PPARgamma resulted in the induction of CLA-1 protein expression in monocytes and in differentiated macrophages. Finally, SR-BI expression is increased in atherosclerotic lesions of apoE-null mice treated with either PPARgamma or PPARalpha ligands. CONCLUSIONS: Our data demonstrate that CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and induced by PPAR activation, identifying a potential role for PPARs in cholesterol homeostasis in atherosclerotic lesion macrophages.

Animals↗

PubMed2000

Immunocytochemical detection of fos protein combined with anterograde tract-tracing using biotinylated dextran.

The present report deals with an axonal tract-tracing procedure in rat enabling visualization of anterogradely transported biotinylated dextran amine (BDA) combined with immnunocytochemical detection of Fos protein following electrical stimulation of the brain. This method allows us to evaluate whether a given structure, receiving both injection of BDA and electrical stimulation, elicits neuronal activation in another part of the brain via direct or indirect projections. We have used the method at the light microscopic level to determine the connectivity of the sensorimotor cortex in the rat. In various parts of the forebrain and brainstem, BDA-labeled fibers originating from the cortex were observed in close apposition to Fos-like immunoreactive cells (FLI) activated by stimulation. This result suggests a direct (probably monosynaptic) projection. On the contrary, FLI neurons were observed in areas devoid of direct afferents, indicating a cascade of activations. The method described in this protocol is applicable for functional anatomy purposes elsewhere within the central nervous system. It constitutes a preliminary step in identifying the validity of a pathway before examination of the reality of the monosynaptic relationship at the electron microscopic level.

Animals↗