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Biomedical subjects

S Besnard

Publications and source records attributed to S Besnard.

15 recordsLinked to original sources
PubMed2004

Do robots need to sleep?

The present paper exposes algorithmic results providing a vision about sleep functions which complements biological theory and experiments. Derived from the algorithmic theory of information, the theory of adaptation aims at quantifying how an inherited or acquired piece of knowledge helps individuals to survive. It gives a scale of complexity for survival problems and proves that some of them can only be solved by a dynamical management of memory associating continuous learning and forgetting methods. In this paper we explain how a virtual robot "Picota" has been designed to simulate the behavior of a living hen. In order to survive in its synthetical environment, our robot must recognize good seeds from bad ones, and should take rest during night periods. Within this frame, and facing the rapid evolution of to-be-recognized forms, the best way to equilibrate the energetic needs of the robot and ensure survival is to use the nightly rest to reorganize the pieces of data acquired during the daily learning, and to trash the less useful ones. Thanks to this time sharing, the same circuits can be used for both daily learning and nightly forgetting and thus costs are lower; however, this also forces the system to "paralyse" the virtual robot, and therefore the night algorithm is reminiscent of paradoxical (REM) sleep. The algorithm of the robot takes advantage of the alternation between wakefulness or activity and the rest period. This diagram quite accurately recalls the REM period. In the future, the convergence between the neurophysiology of sleep and the theory of complexity may give us a new line of research in order to elucidate sleep functions.

Algorithms↗
PubMed2002

Venous stagnation induced by 7 days in HDT, in the cerebral, ophthalmic, renal and splanchnic territories.

The scientific objectives was to quantify the vascular changes in the brain, eye fundus, renal parenchyma, and splanchnic network. Heart, portal, jugular, femoral veins were investigate by Echography. The cerebral mesenteric, renal and ophthalmic arteries were investigated by Doppler. Eye fundus vein an papilla were investigated by optical video eye fundus. The left ventricle volume decreased as usual in HDT. The cerebral and ophthalmic vascular resistances didn't change whereas the eye fundus papilla and vein, and the jugular vein increased. These arterial and venous data confirm the existence of cephalic venous blood stasis without sign of intracranial hypertension. On the other hand the kidney volume increased which is in agreement with blood flow stagnation at this level. At last the mesenteric vascular resistance decreased and the portal vein section increased in HDT which is in favor of an increase in flow and flow volume through the splanchnic area.

Journal Article↗
PubMed2001

Increased ischemia-induced angiogenesis in the staggerer mouse, a mutant of the nuclear receptor Roralpha.

Ror alpha is an orphan nuclear receptor. In homozygous staggerer mutant mice (Ror alpha(sg/sg)), a deletion within the Ror alpha gene leads to an overexpression of inflammatory cytokines. Because inflammation and hypoxia are 2 key stimuli of ischemia-induced angiogenesis, we studied the role of Ror alpha in this setting. Ischemia was induced by ligation of the right femoral artery in C57BL/6 Ror alpha(+/+) and Ror alpha(sg/sg) mice. After 3 and 28 days, angiogenesis was evaluated by microangiography, measurement of capillary density using immunohistochemistry (anti-CD31), and measurement of blood flow by laser Doppler imaging. At day 3, angiographic score and blood flow were similar in Ror alpha(sg/sg) mice and in Ror alpha(+/+) littermates. Conversely, at day 28, Ror alpha(sg/sg) mice showed a significant 2-fold increase in angiographic score and a 3-fold increase in capillary density within the ischemic hindlimb compared with control. Functionally, this coincided with a significant rise in leg perfusion in Ror alpha(sg/sg) mice (0.83+/-0.05 for ischemic/nonischemic leg perfusion ratio) compared with Ror(+/+) mice (0.66+/-0.04, P<0.05). In addition, more extensive angiogenesis in Ror alpha(sg/sg) mice correlated with an increased expression of eNOS protein by 83+/-12% and 71+/-24% at 3 and 28 days, respectively (P<0.05), whereas the level of the antiangiogenic cytokine IL-12 was significantly reduced by 38+/-10% at day 28 (P<0.05). Conversely, no changes in VEGF expression were observed. Our study identifies for the first time a new role for Ror alpha as a potent negative regulator of ischemia-induced angiogenesis.

Animals↗
PubMed2001

Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.

BACKGROUND: Interleukin (IL)-18 is a potent proinflammatory cytokine with potential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown. METHODS AND RESULTS: In the present study, we examined stable and unstable human carotid atherosclerotic plaques retrieved by endarterectomy for the presence of IL-18 using reverse transcription-polymerase chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was highly expressed in the atherosclerotic plaques compared with control normal arteries and was localized mainly in plaque macrophages. IL-18 receptor was also upregulated in plaque macrophages and endothelial cells, suggesting potential biological effects. To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asymptomatic (stable) plaques (P<0.01). CONCLUSIONS: These results suggest, for the first time, a major role for IL-18 in atherosclerotic plaque destabilization leading to acute ischemic syndromes.

Aged↗
PubMed2001

Involvement of interleukin-6 in atherosclerosis but not in the prevention of fatty streak formation by 17beta-estradiol in apolipoprotein E-deficient mice.

Interleukin-6 (IL-6) gene expressed in bone marrow-derived stromal cells and osteoblasts contributes to the state of mineralization and its control by estradiol may be involved in the development of post-menopausal osteoporosis. Since IL-6 is also expressed in the different cell populations of the arterial wall, the purpose of this study was to gain more insight into its involvement in the atherosclerotic process and the atheroprotective effect of estradiol by studying double deficient mice at the apolipoprotein E and IL-6 loci (IL-6(-/-)/E(-/-)). At 1 year of age, IL-6(-/-)/E(-/-) mice showed similar hypercholesterolemia to IL-6(+/+)/E(-/-) mice but presented significantly larger and more calcified lesions. In younger mice (sixteen weeks of age), no significant difference in fatty streaks could be detected in IL-6(+/+)/E(-/-), IL-6(+/-)/E(-/-) and IL-6(-/-)/E(-/-) mice on a normal chow diet. Estrogen supplementation at this age induced a decrease of fatty streak formation in all three genotypes. The combined data indicate that IL-6 expression is involved at the fibrous plaque stage of the atherosclerotic process but does not constitute a direct target for estradiol to prevent fatty streak formation.

Analysis of Variance↗
PubMed2001

In vivo measurement of flavour release from mixed phase gels.

Flavour release was investigated from pure gelatin, pure agarose and mixed gelatin-agarose gels, all containing 25% sucrose and flavoured with p-cymene, ethyl butyrate, pyrazine and ethanol. Gels were characterised by optical microscopy, and rheological techniques to determine phase separation, elastic modulus and melting temperature. Volatile release was measured by monitoring the four volatiles in the expired air from one individual eating the gels, using Atmospheric Pressure Chemical Ionisation-Mass Spectrometry. The release pattern of p-cymene was not affected by gel type. The release of ethanol, ethyl butyrate and pyrazine was affected to different extents by the matrix suggesting that both the properties of the volatile and the matrix determine volatile release in vivo.

Flavoring Agents↗
PubMed2001

3D realtime echography and echography assisted by a robotic arm for investigating astronauts in the ISS from the ground.

As human will stay for long duration in isolated sites like ISS there will be a need to perform quick and reliable diagnosis to evaluate the gravity of the pathology in presence of clinical symptoms. Many pathological situations (abnormal heart rate, pericardic collection, mitral prolaps, cholecystis, renal lithiasis, normal and ectopic pregnancies, ovarian cyst, acute appendicitis, phlebitis ... ) may occur even if all the astronauts are absolutely normal and healthy preflight. Ultrasound echography and Doppler are non invasive methods easy to use in space and very well adapted and used in routine for such diagnosis at the hospital. The objective of the present project was to design a method that guarantee a reliable echographic diagnostic in an isolated site (space station or earth site) by a Medical Doctor located at the expert site that should be the Nasa control center for ISS. It is supposed that there is only a non sonographer person in the isolated site and that the transmission system (audio, video, numeric..) is the only link between the 2 sites. Two options are proposed: (a) A 3D realtime acquisition echograph that can record quickly all the echos of a volume containing the organ suspected to have a lesion, all these echo information being sent to the ground and processed by the ground experts, (b) A robotic arm that hangs the echo probe in the isolated site tele-operated (through sattelite network) from the ground by an expert in clinical ultrasound. (As the expert moves the joystick of his ground computer the robotic arm reproduces the same movements on the probe).

Aerospace Medicine↗
PubMed2000

Transcriptional regulation of apolipoprotein C-III gene expression by the orphan nuclear receptor RORalpha.

Triglyceride-rich remnant lipoproteins are considered as major risk factors contributing to the pathogenesis of atherosclerosis. Because apolipoprotein (apo) C-III is a major determinant of plasma triglyceride and remnant lipoprotein metabolism, it is important to understand how the expression of this gene is regulated. In the present study, we identified the orphan nuclear receptor RORalpha1 as a regulator of human and mouse apo C-III gene expression. Plasma triglyceride and apo C-III protein concentrations in staggerer (sg/sg) mice, homozygous for a deletion in the RORalpha gene, were significantly lower than in wild type littermates. The lowered plasma apo C-III levels were associated with reduced apo C-III mRNA levels in liver and intestine of sg/sg mice. Transient transfection experiments in human hepatoma HepG2, human colonic CaCO2, and rabbit kidney RK13 cells demonstrated that overexpression of the human RORalpha1 isoform specifically increases human apo C-III promoter activity, indicating that RORalpha1 enhances human apo C-III gene transcription. RORalpha1 response elements were mapped by promoter deletion analysis and gel shift experiments to two AGGTCA half-sites located at positions -83/-78 (within the C3P site) and -23/-18 (downstream of the TATA box) in the human apo C-III promoter, with the -23/-18 site exhibiting the highest binding affinity. Transfection of site-directed mutated constructs in HepG2 cells indicated that the RORalpha1 effect is predominantly mediated by the -23/-18 site. This site is conserved in the mouse apo C-III gene promoter. Moreover, RORalpha binds to the equivalent mouse site and activates constructs containing three copies of the mouse site cloned in front of an heterologous promoter. Taken together, our data identify RORalpha as a transcriptional regulator of apo C-III gene expression, providing a novel, physiological role for RORalpha1 in the regulation of genes controlling triglyceride metabolism.

Animals↗
PubMed2000

Therapeutic liver repopulation in a mouse model of hypercholesterolemia.

Liver repopulation constitutes an attractive approach for the treatment of liver disorders or of diseases requiring abundant secretion of an active protein. We have described previously a model of selective repopulation of a normal liver by Fas/CD95-resistant hepatocytes, in which we achieved up to 16% hepatocyte repopulation. In the present study, we investigated the therapeutic efficacy of this strategy. With this aim, apolipoprotein E (ApoE) knockout mice were transplanted with Fas/CD95-resistant hepatocytes which constitutively express ApoE. Transplanted mice were submitted to weekly injections of non-lethal doses of the Fas agonist antibody Jo2. After 8 weeks of treatment, we obtained up to 30% of the normal level of plasma ApoE. ApoE secretion was accompanied by a drastic and significant decrease in total plasma cholesterol, which even fell to normal levels. Moreover, this secretion was sufficient to markedly reduce the progression of atherosclerosis. These results demonstrate the efficacy of this repopulation approach for correcting a deficiency in a protein secreted by the liver.

Animals↗
PubMed2000

Air-contrast sonohysterography as a first step assessment of tubal patency.

We assessed the use of air as a sonographic contrast agent in the investigation of tubal patency by sonohysterography. We examined 115 women assessed for infertility. After saline sonohysterography, small amounts of air were insufflated, and the tubal passage of bubbles was monitored. In five patients (excluded from the results), cervical stenosis prevented the procedure. Ninety-one tubes (right side) and 86 tubes (left side) were definitively patent; 5 and 7, respectively, were probably patent; and 12 and 16, respectively, were nonvisualized. Nine patients had polyps, 3 had synechiae, and 2 had submucosal fibroids. None of the patients had infectious complications. Air-sonohysterography and laparoscopy with chromopertubation showed agreement in 79.4%. In 17.2% of patients, the tubes were considered nonvisualized by air-sonohysterography when they were patent. The sensitivity was 85.7% and specificity 77.2%. In conclusion, air-sonohysterography is a comfortable, simple, and inexpensive first line of tubal patency investigations yielding high accuracy.

Adolescent↗
PubMed1999

Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1.

Interleukin-6 (IL-6) is a pleiotropic cytokine, whose plasma levels are elevated in inflammatory diseases such as atherosclerosis. We have previously reported that peroxisome proliferator-activated receptor alpha (PPARalpha) ligands (fibrates) lower elevated plasma concentrations of IL-6 in patients with atherosclerosis and inhibit IL-1-stimulated IL-6 secretion by human aortic smooth muscle cells (SMC). Here, we show that aortic explants isolated from PPARalpha-null mice display an exacerbated response to inflammatory stimuli, such as lipopolysaccharide (LPS), as demonstrated by increased IL-6 secretion. Furthermore, fibrate treatment represses IL-6 mRNA levels in LPS-stimulated aortas of PPARalpha wild-type, but not of PPARalpha-null mice, demonstrating a role for PPARalpha in this fibrate action. In human aortic SMC, fibrates inhibit IL-1-induced IL-6 gene expression. Furthermore, activation of PPARalpha represses both c-Jun- and p65-induced transcription of the human IL-6 promoter. Transcriptional interference between PPARalpha and both c-Jun and p65 occurs reciprocally, since c-Jun and p65 also inhibit PPARalpha-mediated activation of a PPAR response element-driven promoter. This transcriptional interference occurs independent of the promoter context as demonstrated by cotransfection experiments using PPARalpha, p65, and c-Jun Gal4 chimeras. Overexpression of the transcriptional coactivator cAMP-responsive element-binding protein-binding protein (CBP) does not relieve PPARalpha-mediated transcriptional repression of p65 and c-Jun. Finally, glutathione S-transferase pull-down experiments demonstrate that PPARalpha physically interacts with c-Jun, p65, and CBP. Altogether these data indicate that fibrates inhibit the vascular inflammatory response via PPARalpha by interfering with the NF-kappaB and AP-1 transactivation capacity involving direct protein-protein interaction with p65 and c-Jun.

Animals↗
PubMed1999

Protective role of interleukin-10 in atherosclerosis.

The potential role of anti-inflammatory cytokines in the modulation of the atherosclerotic process remains unknown. Interleukin (IL)-10 has potent deactivating properties in macrophages and T cells and modulates many cellular processes that may interfere with the development and stability of the atherosclerotic plaque. IL-10 is expressed in human atherosclerosis and is associated with decreased signs of inflammation. In the present study, we show that IL-10-deficient C57BL/6J mice fed an atherogenic diet and raised under specific pathogen-free conditions exhibit a significant 3-fold increase in lipid accumulation compared with wild-type mice. Interestingly, the susceptibility of IL-10-deficient mice to atherosclerosis was exceedingly high (30-fold increase) when the mice were housed under conventional conditions. Atherosclerotic lesions of IL-10-deficient mice showed increased T-cell infiltration, abundant interferon-gamma expression, and decreased collagen content. In vivo, transfer of murine IL-10 achieved 60% reduction in lesion size. These results underscore the critical roles of IL-10 in both atherosclerotic lesion formation and stability. Moreover, IL-10 appears to be crucial as a protective factor against the effect of environmental pathogens on atherosclerosis.

Animals↗
PubMed1997

Study of the apoptosis induced in vitro by antitumoral drugs on leukaemic cells.

A flow cytometric method for simultaneous apoptotic cell detection and cell cycle analysis was applied on the U937 cell line. Four antitumoral drugs currently used in the treatment of acute myeloid leukaemia were studied in vitro: DNR, IDR, MITO and Ara-C. Our results show a dissociation between the cytostatic effect (the block in the cell cycle observed for low drug concentrations) and the cytotoxic effect (the induction of apoptosis induced by higher concentrations) for all the tested molecules. Low concentrations of Ara-C induced a block in the S phase while higher concentrations (>10(-7) M) induced apoptosis at the G1-S boundary. Low concentrations of anthracyclines (<40 nM DNR and <20nM IDR) induced a block in G2 without apoptosis. Apoptosis was induced in G1 and/or early S phases by higher concentrations of anthracyclines. The concentration inducing 50% apoptosis (IC50) was found to be, respectively, 200 and 40 nM for DNR and IDR. Analysis of MITO-treated cells showed a parallel increase in the percentages of S phase and apoptotic cells. However, the bivariate analysis showed that apoptosis did occur in a population with G1 DNA content. For two other drugs (CAM and COLC), apoptosis occurred for the same concentrations and in the same phase as the block (in S and G2M, respectively). The IC50 of MITO was found to be 100 nM. Cotreatment of the cells with colchicin and either Ara-C or IDR showed that the passage through mitosis was not necessary for the completion of apoptosis at the G1-S boundary. Short incubations of U937 cells with high concentrations of anthracyclines were found to be efficient in inducing further apoptosis. We conclude that, for all the assayed molecules, the cytotoxic and/or cytostatic effects of the antitumoral drugs tested greatly depend on the concentrations used and that, depending on their in vivo pharmacokinetics, the induction of apoptosis could be an important mechanism of action for some of these drugs.

Acute Disease↗
PubMedDate not supplied

Effect of a venotonic agent on the main arteries and veins during a 5 day HDT.

OBJECTIVE: To evaluate the cardiac, arterial and venous effect of a venotonic drug (Cirkan "Ck") administrated orally daily to 6 subjects in HDT position during 5 days. These subjects underwent a second 5d HDT without Ck treatment one month later. Pre and post HDT the subjects were submitted to a stand test. METHOD: The cardiovascular parameters were measured by echography and Doppler. RESULTS AND DISCUSSION: The Cirkan treatment contributed to reduce the increase in cerebral resistance, and to maintain the lower limb resistance at a higher level than on controls. It reduces the vein section at the extremities (Jugular, femoral) and in the central vein system connected to the right heart (sub hepatics). On the other hand it increases the portal vein section which means that the blood stagnation at the splanchnic level is increased. Despite these arterial and venous significant modifications the clinical and ECG and Blood pressure response to the Stand test was similar in both groups.

Ascorbic Acid↗