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Biomedical subjects

P Faure

Publications and source records attributed to P Faure.

At least 19 recordsLinked to original sources
PubMed2001

2'-deoxyguanosine oxidation is associated with decrease in the DNA-binding activity of the transcription factor Sp1 in liver and kidney from diabetic and insulin-resistant rats.

Over the years, several lines of evidence have emerged supporting the role of oxidative stress in the development of diabetic complications. This could involve the increase in the production of reactive oxygen species and the decrease in antioxidative defense systems. Modulation of the level of intracellular reactive oxygen species is likely to affect the intracellular redox homeostasis, which is crucial for numerous biological events such as the transcriptional activation of genes. In this work we studied the binding of the redox transcription factors Sp1 and NF-kappaB extracted from kidney and liver of streptozotocin diabetic (STZ) and fructose-fed rats using electrophoretic mobility shift (EMSA) assay. In addition, the level in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was assessed within DNA by high performance liquid chromatography with electrochemical detection (HPLC-EC). A decrease in the affinity of Sp1 to DNA was observed in the kidney of STZ rats and fructose-fed rats (15% +/- 8.3 and 54% +/- 6.9, respectively, versus control group set to 100%). This was also found to occur to a lower extent, in the liver. Interestingly, higher levels of 8-oxodGuo, a biomarker of DNA oxidation, were measured in the kidney of diabetic rats. Therefore, the modification in the binding efficiency of Sp1 or NF-kappaB could be related to reactive oxygen species-mediated DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Is there chaos in the brain? I. Concepts of nonlinear dynamics and methods of investigation.

In the light of results obtained during the last two decades in a number of laboratories, it appears that some of the tools of nonlinear dynamics, first developed and improved for the physical sciences and engineering, are well-suited for studies of biological phenomena. In particular it has become clear that the different regimes of activities undergone by nerve cells, neural assemblies and behavioural patterns, the linkage between them, and their modifications over time, cannot be fully understood in the context of even integrative physiology, without using these new techniques. This report, which is the first of two related papers, is aimed at introducing the non expert to the fundamental aspects of nonlinear dynamics, the most spectacular aspect of which is chaos theory. After a general history and definition of chaos the principles of analysis of time series in phase space and the general properties of chaotic trajectories will be described as will be the classical measures which allow a process to be classified as chaotic in ideal systems and models. We will then proceed to show how these methods need to be adapted for handling experimental time series; the dangers and pitfalls faced when dealing with non stationary and often noisy data will be stressed, and specific criteria for suspecting determinism in neuronal cells and/or assemblies will be described. We will finally address two fundamental questions, namely i) whether and how can one distinguish, deterministic patterns from stochastic ones, and, ii) what is the advantage of chaos over randomness: we will explain why and how the former can be controlled whereas, notoriously, the latter cannot be tamed. In the second paper of the series, results obtained at the level of single cells and their membrane conductances in real neuronal networks and in the study of higher brain functions, will be critically reviewed. It will be shown that the tools of nonlinear dynamics can be irreplaceable for revealing hidden mechanisms subserving, for example, neuronal synchronization and periodic oscillations. The benefits for the brain of adopting chaotic regimes with their wide range of potential behaviours and their aptitude to quickly react to changing conditions will also be considered.

Animals↗
PubMed2001

Heat stress protects against electrophysiological damages induced by acute doxorubicin exposure in isolated rat hearts.

The use of anthracycline antibiotics as anticancer agents is limited by their cardiac toxicity. Heat stress (HS) is known to confer protection against various myocardial injuries such as ischemia-reperfusion induced damage. This cardioprotective mechanism is associated with an increase in endogenous antioxidative defenses and heat stress proteins (HSPs) synthesis. The aim of this study was thus to investigate whether HS could protect against acute doxorubicin cardiotoxicity using the isolated rat heart model. Rats were either heat stressed (42 degrees C for 15 min) or sham anesthetized. 24 h later, their hearts were isolated and retrogradely perfused at constant flow. Following 30-min of stabilization, hearts were perfused during 70 min with modified-Krebs solution containing 6 mg/l doxorubicin. Control hearts were perfused under identical conditions but without doxorubicin. Different hemodynamic and electrophysiological parameters were assessed in hearts from the four experimental groups. Doxorubicin exposure decreased left ventricular developed pressure (approximately -60% of baseline) and increased coronary perfusion pressure (approximately +230% of baseline). Prior HS did not modify these effects. Incidence of ventricular fibrillation (VF) was significantly enhanced by doxorubicin exposure (66% vs 0% in control group). Moreover, the ventricular action potential duration (APD) was significantly shortened in the presence of doxorubicin. Prior HS prevented both increase in VF incidence and shortening of APD. We conclude that prior heat stress protects myocardium against electrophysiological injury, but not against hemodynamic damage, induced by acute doxorubicine exposure. Further investigations are required to elucidate the precise mechanisms involved in this effect.

Animals↗
PubMed2001

Evaluation of current practices in surgical antimicrobial prophylaxis before and after implementation of local guidelines.

The aim of antibiotic prophylaxis (ABP) is to prevent or at least decrease the incidence of postoperative surgical wound infections. In 1992 and 1995, ABP was the subject of two French consensus conferences. Following these conferences, the local Antibiotics Committee of Hopital Saint-Louis has undertaken a study to evaluate and eventually improve the current practices of ABP. This study was carried out in three steps: a first survey of ABP, the writing of local ABP guidelines and a second survey of ABP after the implementation of these recommendations. Concerning all surgical wards, the first survey found 69% (N = 100/145) of ABP practice is to be inappropriate vs. 18% (N = 25/139) in the second survey. Indications, choice of drugs, selection of dosage, administration timing and treatment duration were significantly improved in the second survey. Writing and implementing local recommendations promoted a more rational use of ABP. In addition, this study allowed Saint-Louis Hospital to set up recommendations for plastic surgery; such recommendations are poorly described in the literature.

Adolescent↗
PubMed2001

Free osteocutaneous scapular apophysis flap for reconstruction of the lateral malleolus.

Lateral malleolus avulsion is uncommon, and fusion of the syndesmosis of the ankle joint is usually performed in such cases. Others have reported successful reconstruction of the lateral malleolus with a vascularized fibular head. A case of reconstruction in a 17-year-old girl, with a free scapular apophysis flap, is presented and compared with alternative flaps available. The anatomy and development of the scapular crest with its cartilaginous apophysis are discussed.

Adolescent↗
PubMed2001

Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma.

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Amiodarone↗
PubMed2001

Cysteinyl leukotrienes modulate angiotensin II constrictor effects on aortas from streptozotocin-induced diabetic rats.

Angiotensin II (Ang II) is a vasopressor peptide involved in the pathogenesis of cardiovascular diseases associated with diabetes mellitus. We have previously reported that the 5-lipoxygenase-derived products, particularly the cysteinyl leukotrienes (CysLTs), are involved in Ang II-induced contraction. In this study, we demonstrated that CysLTs contribute to the contraction elicited by Ang II in isolated aortas from streptozotocin-induced diabetic (SS) rats but not from insulin-treated diabetic rats, fructose-fed rats, or control rats. In an organ bath, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 micromol/L) reduced by 37.6+/-8.2% and 30.1+/-10.9% the Ang II-induced contractions in intact and endothelium-denuded aortic rings, respectively, from SS rats. In contrast, the CysLT(1) receptor antagonist (MK571, 1 micromol/L) or the dual CysLT(1)/CysLT(2) receptor antagonist (BAY-u9773, 0.1 micromol/L) did not affect Ang II-induced contraction. In addition, Ang II induced a 6.2+/-1.5-fold increase in CysLT release through the stimulation of the Ang II type 1 receptor. Furthermore, the urinary excretion of leukotriene E(4) was increased in SS rats (leukotriene E(4), 13.7+/-2.9 ng/24 h [SS rats, n=10] versus 1.5+/-0.5 ng/24 h [control rats, n=6]; P<0.0004). These data suggest the activation of the 5-lipoxygenase pathway in SS rats and the involvement of 5-lipoxygenase-derived products, particularly the CysLTs, in Ang II-induced contraction in aortas from SS rats through stimulation of CysLT receptors different from the well-characterized CysLT(1) or CysLT(2) receptor.

Angiotensin II↗
PubMed2001

In vitro free radical scavenging capacity of thyroid hormones and structural analogues.

It was reported that thyroid hormones decreased Cu(2+)-induced low-density lipoprotein (LDL) oxidation in vitro. Here, we investigated free radical scavenging capacities of thyroid hormones (3,5,3'-tri-iodo-L-thyronine (T(3)), thyroxine (T(4)) and 3,3',5'-tri-iodo-L-thyronine (rT(3))) and structural analogues (L-thyronine (T(0)), 3,5,3'tri-iodothyroacetic acid (TA(3)) and 3,5,3',5'-tetra-iodothyroacetic acid (TA(4))), using three different models of free radical generation. T(0), T(3) and TA(3) slowed down production of conjugated diene and thiobarbituric acid-reactive substances during LDL oxidation by 2,2'-azobis-[2-amidinopropane] (water-soluble), whereas rT(3), T(4) and TA(4) had practically no effect. In this system, T(0) was the more active compound. Using a 1,1-diphenyl-2-picrylhydrazyl (lipid-soluble) test, all compounds also revealed free radical scavenging capacities, but rT(3), T(4) and TA(4) were more active than T(0), T(3) and TA(3). T(3) was able to scavenge superoxide anion and hydroxyl radicals generated in an aqueous phase by a xanthine-xanthine oxidase system, as measured by electron paramagnetic resonance spectroscopy. It may be concluded that: (1) thyroid hormones and analogues with a 4'-hydroxy diphenylether structure have free radical scavenging capacities, (2) this property is influenced by the number of iodines on the phenolic ring, and (3) thyroid hormone scavenging capacity should not be the only mechanism explaining their protective effect on Cu(2+)-induced LDL oxidation. The physiological significance of the findings is discussed.

Analysis of Variance↗
PubMed2001

[Glucose and redox sensitive transcription factors: consequences on the insulin receptor].

During diabetes an oxidizing stress can be observed, whose origins are multiple. This stress can be regarded as a particular messenger, certainly modifying the transduction of the insulinic signal but also the activity of certain transcription factors. Indeed NF-kappa B activity is increased, while Sp1 activity drops in this context. NF-kappa B activation takes certainly part in vascular remodeling and plays a role in the genesis of the oxidative stress. Hence, NF-kappa B activity precociously increases in the states of insulin resistance before hyperglycemia sets in. Sp1 undergoes a significant fall in activity in the presence of glucose. This activity can be restored by antioxydants in the cell culture medium, Sp1 being necessary to insulin receptor expression, the question arises whether this drop in activity modifies significantly the insulin expression.

Arteriosclerosis↗
PubMed2000

Synaptic efficacy and the transmission of complex firing patterns between neurons.

In central neurons, the summation of inputs from presynaptic cells combined with the unreliability of synaptic transmission produces incessant variations of the membrane potential termed synaptic noise (SN). These fluctuations, which depend on both the unpredictable timing of afferent activities and quantal variations of postsynaptic potentials, have defied conventional analysis. We show here that, when applied to SN recorded from the Mauthner (M) cell of teleosts, a simple method of nonlinear analysis reveals previously undetected features of this signal including hidden periodic components. The phase relationship between these components is compatible with the notion that the temporal organization of events comprising this noise is deterministic rather than random and that it is generated by presynaptic interneurons behaving as coupled periodic oscillators. Furthermore a model of the presynaptic network shows how SN is shaped both by activities in incoming inputs and by the distribution of their synaptic weights expressed as mean quantal contents of the activated synapses. In confirmation we found experimentally that long-term tetanic potentiation (LTP), which selectively increases some of these synaptic weights, permits oscillating temporal patterns to be transmitted more effectively to the postsynaptic cell. Thus the probabilistic nature of transmitter release, which governs the strength of synapses, may be critical for the transfer of complex timing information within neuronal assemblies.

Animals↗
PubMed1999

Heat stress fails to protect myocardium of streptozotocin-induced diabetic rats against infarction.

OBJECTIVE: Protection conferred by heat stress (HS) against ischaemia-reperfusion injury, in term of mechanical function and myocardial necrosis, has been extensively studied. In contrast, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated heart and on the myocardial heat stress protein (HSP) 72 synthesis, in a model of insulin-dependent diabetic rats. METHODS: Three groups of animals were studied: D rats were rendered diabetic by 55 mg/kg streptozotocin i.v. injection. DI rats received the same treatment plus a daily injection of insulin started 2 weeks after and V rats received the vehicle of streptozotocin plus a daily injection of saline. Eight weeks later, D, DI and V rats were either heat-stressed (42 degrees C for 15 min) or sham-anaesthetised. Twenty-four hours later, their hearts were isolated, perfused using the Langendorff technique, and subjected to a 30 min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using an electrophoresis coupled with a Western blot analysis. RESULTS: Infarct-to-risk ratio (I/R) was significantly reduced in hearts from heat-stressed (11.7 +/- 2.0%) compared to sham (30.0 +/- 3.2%) V rats. This cardioprotection was not observed in hearts from D (I/R: 31.4 +/- 3.3 vs. 34.3 +/- 3.5%) and DI (I/R: 28.7 +/- 1.6 vs. 30.3 +/- 1.6%) rats. Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the six experimental groups. Western blot analysis of the myocardial HSP72 content showed a comparable heat stress-induced increase of this protein, in V, D and DI animals. CONCLUSION: These results demonstrate that myocardial protective effect induced by heat stress could not extend to a pathological animal model like the diabetic rat and seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the heat stress proteins in this adaptive response.

Analysis of Variance↗
PubMed1999

Effects of 8-oxo-7,8-dihydro-2'-deoxyguanosine on the binding of the transcription factor Sp1 to its cognate target DNA sequence (GC box).

Emphasis was placed in this work on the assessment of the role of guanine bases in the interaction of transcription factor SP1 with its cognate DNA sequence. For this purpose, each guanine residue of the 5'-GGGGCG-GGG-3' (GC box) target DNA sequence was substituted in turn by 8-oxo-7,8-dihydro-2'-deoxyguanosine. The latter oxidized nucleotide which is likely to be present in mammalian DNA and exhibit mutogenic features is expected to be involved in age-related diseases and cancer. The effect of the incorporation of 8-oxodGuo into DNA on the binding of transcription factor Sp1 was studied using electrophoretic mobility shift assays with nuclear extracts from HeLa cells. When guanines at position G '2, G '3, G '4, G '5 and G'6 were replaced with 8-oxodGuo, binding of Sp1 was only 28%, 30%, 7%, 5% and 21%, respectively, to that of the non-substituted oligonucleotide. The binding is less affected when guanines at position G'1, G'7, G'8 and G'9 were substituted by 8-oxodGuo. Results show up the importance of the core of the GC box and the stronger contribution of the second and the third zinc finger to the binding with DNA. All together, this suggests that incorporation of 8-oxodGuo may alter the expression of the gene regulated by Sp1 and affect the response of the cell.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.

Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.

Animals↗
PubMed1999

[Dermatologic consultation in a precarious situation: a prospective medical and social study at the Hôpital Saint-Louis in Paris].

INTRODUCTION: The aim of our study was to evaluate the outcomes and the cost of the dermatological consultation for poor and destitute patients, in Saint-Louis Hospital. PATIENTS AND METHODS: We carried out a prospective study from May to October 1996. One hundred and eighty-nine patients (237 consultations) who had no social welfare, were examined. RESULTS: They revealed that 82 p. 100 were male, 63.7 p. 100 were French, 13.9 p. 100 came from Maghreb, 9.7 p. 100 from Sub-Saharan Africa, 73 p. 100 were homeless and 25.7 p. 100 were alcoholic. The average age was around 37.6. The main medical disorders: scabies (56.5 p. 100), lice (22.4 p. 100) and cutaneous infections (7.2 p. 100) were related to the patients' living conditions and their social and economic situation. The other diseases observed were identical to the ones detected in regular health care centers. Complementary laboratories were necessary in 9.3 p. 100 consultations. Only 2 p. 100 of patients were admitted in Hospital. Local treatment was applied by nurses in 67 p. 100 of cases. Drugs were delivered free of charge by the Hospital's pharmacy in 64 p. 100 of cases. The cost of drugs was 83 FF per patient. The mean of duration of treatment was 10.5 days. DISCUSSION: Social workers are a key element in helping the patients to recover their social rights (49 p. 100 of patients have recovered social rights after 6 months). The frequency of skin diseases is higher in this population than in general population, especially in homeless persons. Access to health care is a problem of public health.

Adult↗