Biomedical subjects

P André

Publications and source records attributed to P André.

At least 19 recordsLinked to original sources

PubMed2006

Three-year increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and women: the D.E.S.I.R. cohort.

AIMS/HYPOTHESIS: Among hepatic markers, gamma-glutamyltransferase (GGT) is the main predictor for development of type 2 diabetes, but there are no data to date on changes in GGT and type 2 diabetes incidence. METHODS: Data at baseline and at 3 years from the D.E.S.I.R. cohort were used, comprising 2,071 men and 2,130 women without baseline diabetes. RESULTS: Changes in GGT level were correlated with changes in markers of insulin resistance (fasting insulin, homeostasis model assessment of insulin resistance), as well as with the following elements of the metabolic syndrome: central obesity, and increased fasting glucose, triglycerides and blood pressure (systolic and diastolic). The 3-year increase in GGT was associated with incident type 2 diabetes in both sexes, after adjusting for age and baseline GGT. After further adjustment for baseline confounding factors, including alanine-aminotransferase, alcohol intake, obesity and fasting insulin, the odds ratios (95% CI) for an association between incident type 2 diabetes and unchanged or increased (as opposed to decreased) GGT levels were 2.54 (1.38-4.68) in men (p=0.003) and 2.78 (1.20-6.42) in women (p=0.02). These associations were slightly attenuated after adjusting for the 3-year change in BMI, alcohol consumption and fasting insulin, the odds ratios being 2.49 (1.28-4.86) in men and 2.53 (1.01-6.40) in women. This relationship was not dependent on intra-individual variability. CONCLUSIONS/INTERPRETATION: An unchanged or increased GGT level over time, even when GGT is in the normal range, is correlated with increasing insulin resistance and is associated with a risk of incident type 2 diabetes in both sexes, independently of baseline GGT, which is itself a diabetes risk factor.

Body Mass Index↗

PubMed2006

Cyclin dependent kinase inhibitors prevent apoptosis of postmitotic mouse motoneurons.

Recent evidence suggests that apoptosis in post-mitotic neurons involves an aborted attempt of cells to re-enter the cell cycle which is characterized by increased expression of cyclins, such as cyclin D1, prior to death. However, such cyclins activation prior to apoptotic cell death remains controversial. Many neurological disorders are characterized by neuronal loss, particularly amyotrophic lateral sclerosis (ALS). ALS is a motoneuronal degenerative condition in which motoneuron loss could be due to an inappropriate return of these cells in the cell cycle. In the present study, we observed that deprivation of neurotrophic factor in purified motoneuron cultures induces an apoptotic pathway. After neurotrophic factor withdrawal, DAPI (4,6-diamidin-2-phenylindol dichlorohydrate) staining revealed the presence of nuclear condensation, DNA fragmentation, and perinuclear apoptotic body. Similarly, release of apoptotic microparticles and activation of caspases-3 and -9 were observed within the first hours following neurotrophic factor withdrawal. Next, we tested whether inhibition of cell cycle-related cyclin-dependent kinases (cdks) can prevent motoneuronal cell death. We showed that three cdk inhibitors, olomoucine, roscovitine and flavopiridol, suppress the death of motoneurons. Finally, we observed early increases in cyclin D1 and cyclin E expression after withdrawal of neurotrophic factors. These findings support the hypothesis that after removal of trophic support, post-mitotic neuronal cells die due to an attempt to re-enter the cell cycle in an uncoordinated and inappropriate manner.

Animals↗

PubMed2005

Hepatic markers and development of type 2 diabetes in middle aged men and women: a three-year follow-up study. The D.E.S.I.R. Study (Data from an Epidemiological Study on the Insulin Resistance syndrome).

AIM: It has been shown, mainly in men, that gamma-glutamyltransferase (gammaGT) and alanine-aminotransferase (ALT) predict the development of type 2 diabetes. This study investigates the association between hepatic markers and the 3-year risk of diabetes. METHODS: Incident diabetes was studied in 2071 men and 2130 women without diabetes at baseline from the D.E.S.I.R. cohort. RESULTS: Adjusting on age, only gammaGT was predictive of diabetes in both sexes, whereas ALT and aspartate-aminotransferase (AST) were only predictive in men, and bilirubin was not predictive. After adjustment on classical confounding factors and on ALT activity, the odds ratios (OR) for incident diabetes increased across baseline gammaGT quartiles: 1, 3.1, 2.6, 5.0 in men (P<0.0003) and 1, 0.9, 3.2, 3.5 in women (P<0.01). The relations with ALT and AST were not significant after adjusting on gammaGT. Additional adjustment on markers of insulin resistance, BMI or fasting plasma glucose attenuated the risk associated with gammaGT in both sexes, and it remained significantly predictive only in the men. Pooling men and women, those with gammaGT above the median had adjusted ORs of developing diabetes of 13.7 (1.8-99.8) if WHR > =0.85 and 1.7 (0.6-4.8) if WHR<0.85 (interaction P<0.007). CONCLUSION: gammaGT was the main hepatic risk marker for type-2 diabetes in both sexes, especially in subjects with central adiposity.

Biomarkers↗

PubMed2004

[Mycobacterium fortuitum skin infection occurring after a facelift].

INTRODUCTION: Mycobacterium fortuitum skin infections are rare and usually iatrogenic. We report a case with cervical involvement following a facelift. OBSERVATION: A 65 year-old woman, without past history, underwent bilateral surgical facelift, complicated by cutaneous necrosis and treated with directed healing at home. Six weeks later, an abscessed nodule appeared under the left maxillary and was drained surgically. Then other pre-auricular and left cervical inflammatory nodules appeared without adenopathy or fever. M. fortuitum was isolated in bacteriological samples. The initially probabilistic antibiotherapy with carithromycin, subsequently adapted with amikacine and cirprofloxacine and then imipeneme for a total duration of 3 months, led to the clinical cure. DISCUSSION: Mycobacterium fortuitum is a rapidly growing, ubiquitous, mycobacteria responsible for nosocomial infections in immunocompetent patients, notably following plastic surgery. Contamination occurs where there has been a rupture in the skin barrier through contact with a vector (water, surgical material, antiseptic.). Treatment, which is not codified, consists in the association of surgery and antibiotics for several months.

Aged↗

PubMed2004

Evaluation of the safety of a non-animal stabilized hyaluronic acid (NASHA -- Q-Medical, Sweden) in European countries: a retrospective study from 1997 to 2001.

BACKGROUND: In Europe, several filler devices are currently on the market for use in aesthetic dermatology and some of them cause severe, permanent, adverse reactions. Since 1996 a non-animal stabilized hyaluronic acid (NASHA) from Q-Medical, Sweden, has been introduced and is becoming a leading product in aesthetic dermatology. Hyaluronic acid has no species specificity and skin testing is not recommended before treatment. OBJECTIVE: Our purpose was to evaluate the incidence of adverse reactions from 1997 to 2001 and the safety of NASHA after injections into the skin for aesthetic reasons. METHOD: Surveys were sent to physicians in European countries that agreed to participate. This is a retrospective study. A total of 12 344 syringes were sold by the Q-Medical to these physicians and we evaluated the total number of patients treated to 35% of this number (4320). We separated immediate hypersensitivity reactions from delayed reactions and analysed infectious and other types of reactions. RESULTS: From 1997 until 2001, 34 cases of hypersensitivity were reported: 16 cases of immediate hypersensitivity and 18 cases of delayed. The global risk of sensitivity is 0.8%. Since 2000, the amount of protein in the raw product has decreased and the incidence of hypersensitivity reactions is around 0.6%. As 50% of these reactions are immediate and resolved within less than 3 weeks, the risk of strong but transient, delayed reaction is around 0.3%. Four cases of abscess were reported. They were all sterile. No bacterial infection was found. Herpetic recurrence is possible after lip augmentation according to the technique of injection. No systemic reactions were reported. CONCLUSION: NASHA is a very useful and safe filler product. Skin testing does not seem to be necessary.

Biocompatible Materials↗

PubMed2003

[The adipocyte in the history of slimming agents].

Nowadays, in industrialised societies, it is fashionable for women to be slim. However, throughout history, this has not always been the case, especially as "cellulite" (cellulitis) was full of typically feminine symbols. The ideal feminine silhouette has changed with the rhythm of cultures. Cellulitis is an inappropriate term used by women to describe curves which they judge to be too plump and not very aesthetic, mostly around the thighs and hips. This lipodystrophy of the adipose tissue represents approximately 25% of a woman's body weight. It is clinically characterised by an "orange peel" skin surface, which is a result of the excessive development of the volume of the adipocytes organised in lobules within the walls of the unstretchable conjunctive tissue. This phenomenon is associated with an insufficiency of the venous tonus and an increase in the capillary permeability, which both contribute to an increase in the infiltration of water in the tissue. In reality, the understanding of cellulite has truly progressed with research based on adipocyte functions. An adipocyte is a metabolically active cell which plays a central role in the control of the energetic balance of the organism. In order to assume this role, it possesses all the enzymatic equipment necessary for synthesis (lipogenesis) and for triglyceride storage, mobilisation and liberation as free fatty acids (lipolysis). During these last few years, as well as this role as an energetic reserve which manages lipogenesis/lipolysis balance, the adipocyte has acquired the status of an endocrine and paracrine cell through the identification of numerous secreted factors. When we look back at the history of slimming products launched on the market since the 1980's, we can notice the role of the adipocyte tool and understand its functions in the choice of active ingredients, the development of complementary actions, the importance of the texture, the evolution of methods used to evaluate the efficacy on human volunteers and of course, we must not forget the women satisfaction and the power of seduction through words.

Adipocytes↗

PubMed2002

Clopidogrel-induced qualitative changes in thrombus formation correlate with stent patency in injured pig cervical arteries.

Thienopyridines (ticlopidine or clopidogrel) alone or in combination with aspirin are now the reference antiplatelet therapy after stent implantation. To better understand the high efficacy and low risk of bleeding with these agents, we tested clopidogrel alone or with aspirin in an acute ex vivo flow chamber model and in a subacute in vivo arterial thrombosis model. Clopidogrel induced a dose-dependent increase in bleeding time (BT), inhibited ADP-induced platelet aggregation and in the flow chamber reduced thrombus size, and changed thrombus structure to broad-based structure composed of nondegranulated loosely attached platelets contrasting with the tight clumps of degranulated platelets seen without clopidogrel. The in vivo model involved angioplasty and stenting at the site of a preinduced arterial lesion and thrombosis in pig carotid arteries. Clopidogrel alone or with aspirin (but not aspirin alone) decreased the number of stented vessels occluded for more than 24 h and conversely reduced the number of occluding thrombus. At 96 h after stenting, 100% and 90% of the arteries were patent with clopidogrel/aspirin and clopidogrel alone, respectively (vs. 67% and 44% with aspirin and saline, respectively). Clopidogrel destabilizes thrombus without complete abolishment of platelet reactivity.

Animals↗

PubMed2002

Facial lipoatrophy: report of five cases after injection of synthetic filler into naso-labial folds.

BACKGROUND: Facial lipoatrophies are rare disfiguring syndromes, most commonly characterized by loss of buccal fat pads. AIMS: To demonstrate a relationship between facial lipoatrophy and a new synthetic filler device (Profill) used to correct naso-labial folds. METHODS: Five cases of lipoatrophy, appeared 9 months or later after Profill injections. No systematic abnormalities were found. In one case biopsy reported a destruction of adipocytes with intense fibrosis in the hypodermis. DISCUSSION: The culpability of this new biodegradable product is highlighted. To our knowledge, this is the first time this adverse reaction has been reported. CONCLUSION: Serious adverse reactions may appear months after Profill injection, skin testing is not always predictive or sufficient. Clinical studies with long-term follow-up need to be carried out before new filler devices are launched on the market.

Adult↗

PubMed2002

Characterization of low- and very-low-density hepatitis C virus RNA-containing particles.

The presence of hepatitis C virus (HCV) RNA-containing particles in the low-density fractions of plasma has been associated with high infectivity. However, the nature of circulating HCV particles and their association with immunoglobulins or lipoproteins as well as the characterization of cell entry have all been subject to conflicting reports. For a better analysis of HCV RNA-containing particles, we quantified HCV RNA in the low-density fractions of plasma corresponding to the very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) fractions from untreated chronically HCV-infected patients. HCV RNA was always found in at least one of these fractions and represented 8 to 95% of the total plasma HCV RNA. Surprisingly, immunoglobulins G and M were also found in the low-density fractions and could be used to purify the HCV RNA-containing particles (lipo-viro-particles [LVP]). Purified LVP were rich in triglycerides; contained at least apolipoprotein B, HCV RNA, and core protein; and appeared as large spherical particles with a diameter of more than 100 nm and with internal structures. Delipidation of these particles resulted in capsid-like structures recognized by anti-HCV core protein antibody. Purified LVP efficiently bind and enter hepatocyte cell lines, while serum or whole-density fractions do not. Binding of these particles was competed out by VLDL and LDL from noninfected donors and was blocked by anti-apolipoprotein B and E antibodies, whereas upregulation of the LDL receptor increased their internalization. These results suggest that the infectivity of LVP is mediated by endogenous proteins rather than by viral components providing a mechanism of escape from the humoral immune response.

Hepacivirus↗

PubMed2001

Oxidized low-density lipoprotein promotes mature dendritic cell transition from differentiating monocyte.

Proinflammatory oxidized phospholipids are generated during oxidative modification of low-density lipoproteins (LDL). The production of these proinflammatory oxidized phospholipids is controlled by secreted enzymes that circulate as proteins complexed with LDL and high-density lipoprotein. During the acute phase response to tissue injury, profound changes occur in lipoprotein enzymatic composition that alter their anti-inflammatory function. Monocytes may encounter oxidized phospholipids in vivo during their differentiation to macrophages or dendritic cells (DC). In this study we show that the presence of oxidized LDL (oxLDL) at the first day of monocyte differentiation to DC in vitro yielded phenotypically atypical cells with some functional characteristics of mature DC. Addition of oxLDL during the late stage of monocyte differentiation gave rise directly to phenotypically mature DC with reduced uptake capacity, secreting IL-12 but not IL-10, and supporting both syngeneic and allogeneic T cell stimulation. In contrast to known mediators of DC activation, oxLDL did not trigger maturation of immature DC. An intriguing possibility is that a burst of oxidized phospholipids is an endogenous activation signal for the immune system, which is tightly controlled by lipoproteins during the acute phase response.

Cell Differentiation↗

PubMed2001

CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression.

OBJECTIVE AND DESIGN: We have recently shown that the number of CCR5 molecules at the surface of peripheral blood CD4 T cells (CCR5 density) correlates with the viral RNA plasma level in HIV-1-infected individuals. As viral load is a strong predictor of outcome in HIV infection, the present study examines the correlation between CCR5 density and HIV-1 disease progression. METHODS: Using a quantitative flow cytometry assay, we measured CCR5 density in HIV-1-infected adults and control healthy volunteers. The CCR5 genotype (presence of a Delta 32 allele) was also determined. RESULTS: CCR5 density was stable over time on non-activated, HLA-DR(-)CD4 T cells of infected individuals. In a study cohort of 25 patients, asymptomatic and non-treated, we observed a correlation between CCR5 density on HLA-DR(-)CD4 T cells and the CD4 T cell slope (P = 0.026), which was independent of the presence or absence of the Delta 32CCR5 deletion. In particular, slow progressors expressed lower CCR5 densities than non-slow progressors (P = 0.004) and non-infected control subjects (P = 0.002). CONCLUSION: These results are compatible with the hypothesis that CCR5 density, which is a key factor of HIV-1 infectability, determines in-vivo HIV production, and thereby the rate of CD4 cell decline. Consequently, CCR5 density quantitation could be a new valuable prognostic tool in HIV-1 infection. Moreover, these data emphasize the therapeutic potential of treatments that reduce functional CCR5 density.

Adult↗

PubMed2001

Localized reduction of atherosclerosis in von Willebrand factor-deficient mice.

To examine the role of the platelet adhesion molecule von Willebrand factor (vWf) in atherogenesis, vWf-deficient mice (vWf-/-) were bred with mice lacking the low-density lipoprotein receptor (LDLR-/-) on a C57BL/6J background. LDLR-/-vWf+/+ and LDLR-/-vWf-/- mice were placed on a diet rich in saturated fat and cholesterol for different lengths of time. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules in both genotypes, indicating an increase in P-selectin-mediated adhesion to the endothelium. After 8 weeks on the atherogenic diet, the fatty streaks formed in the aortic sinus of LDLR-/-vWf-/- mice of either sex were 40% smaller and contained fewer monocytes than those in LDLR-/-vWf+/+ mice. After 22 weeks on the atherogenic diet (early fibrous plaque stage), the difference in lesion size in the aortic sinus persisted. Interestingly, the lesion distribution in the aortas of LDLR-/-vWf-/- animals was different from that of LDLR-/- vWf+/+ animals. In vWf-positive mice, half of all lesions were located at the branch points of the renal and mesenteric arteries, whereas lesions in this area were not as prominent in the vWf-negative mice. These results indicate that the absence of vWf primarily affects the regions of the aorta with disturbed flow that are prone to atherosclerosis. Thus, vWf may recruit platelets/leukocytes to the lesion in a flow-dependent manner or may be part of the mechano-transduction pathway regulating endothelial response to shear stress.

Animals↗

PubMed2001

Protection against experimental autoimmune encephalomyelitis by a proteasome modulator.

The capacity of interferon beta to alter the course of multiple sclerosis has promoted a new therapeutic concept, based upon the modulation of the immune response rather than its suppression. As the proteasome plays a crucial role in the control of the inflammatory process and immune cell survival, targeting the proteasome appears as a novel approach for the prevention and treatment of inflammatory autoimmune diseases. We have previously shown that ritonavir, an HIV-1 protease inhibitor used in AIDS therapy, can modulate the proteasome function by inhibiting the chymotrypsin-like activity and enhancing the trypsin-like activity. We have, therefore, explored its therapeutic potential on experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis, in Lewis rats and SJL mice. Daily administration of ritonavir during autoimmune antigen stimulation prevented clinical symptoms of EAE in a dose- and time-dependent manner. This protection was accompanied by an inhibition of the mononuclear cell infiltration into the central nervous system usually observed in EAE. Despite a complete absence of clinical symptoms during first EAE induction, ritonavir-treated animals became resistant to further induction of EAE, suggesting an immune mechanism of protection. These results suggest that proteasome modulation using ritonavir or analogues may be of interest for patients with multiple sclerosis.

Animals↗

PubMed2001

CD antigens 2001.

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Antigens, CD↗

PubMed2001

Transport properties in a two-temperature plasma: theory and application.

An alternate derivation of transport properties in a two-temperature plasma has been performed. Indeed, recent works have shown that the simplified theory of transport properties out of thermal equilibrium introduced by Devoto and then Bonnefoi, very often used in two-temperature modeling, is questionable and particularly does not work when calculating the combined diffusion coefficients of Murphy. Thus, in this paper, transport properties are derived without Bonnefoi's assumptions in a nonreactive two-temperature plasma, assuming chemical equilibrium is achieved. The electron kinetic temperature T(e) is supposed to be different from that of heavy species T(h). Only elastic processes are considered in a collision-dominated plasma. The resolution of Boltzmann's equation, thanks to the Chapman-Enskog method, is used to calculate transport coefficients from sets of linear equations. The solution of these systems allows transport coefficients to be written as linear combinations of collision integrals, which take into account the interaction potential for a collision between two particles. These linear combinations are derived by extending the definition and the calculation of bracket integrals introduced by Chapman et al. to the thermal nonequilibrium case. The obtained results are rigorously the same as those of Hirschfelder et al. at thermal equilibrium. The derivation of diffusion velocity and heat flux shows the contribution of a new gradient, that of the temperature ratio straight theta=T(e)/T(h). An application is presented for a two-temperature argon plasma. First, it is shown that the two-temperature linear combinations of collision integrals are drastically modified with respect to equilibrium. Secondly, the two-temperature simplified theory of transport coefficients of Devoto and Bonnefoi underestimates the electron thermal conductivity with respect to the accurate value at T(e)=20 000 K. Lastly, contrary to the simplified theory of transport coefficients, the diffusion coefficients satisfy the symmetry conditions. An example is given at T(e)=6000 K for different values of straight theta for the diffusion coefficient between electrons and heavy species D(e-Ar) as well as for that between argon atoms and argon ions D(Ar-Ar+).

Journal Article↗

PubMed2001

Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice.

Stimulation of endothelial cells by various inflammatory mediators leads to release of Weibel--Palade bodies and therefore to exocytosis of both P-selectin (adhesion receptor for leukocytes) and von Willebrand factor (vWf) (platelet ligand). The potential role of vWf in leukocyte recruitment was investigated with the use of vWf-deficient mice. We report a strong reduction of leukocyte rolling in venules of vWf-deficient mice. Similarly, vWf deficiency led to a decrease in neutrophil recruitment in a cytokine-induced meningitis model as well as in early skin wounds. In all instances with an antibody that preferentially recognizes plasma membrane P-selectin, we observed a dramatic reduction in P-selectin expression at the cell surface of vWf-deficient endothelium. With confocal microscopy, we found that the typical rodlike shape of the Weibel--Palade body is missing in vWf -/- endothelial cells and that part of the P-selectin content in the vWf -/- cells colocalized with LAMP-1, a lysosomal marker. However, intracellular P-selectin levels were similar in tumor necrosis factor alpha- and lipopolysaccharide-activated cells of both genotypes. We conclude that the absence of vWf, as found in severe von Willebrand disease, leads to a defect in Weibel--Palade body formation. This defect results in decreased P-selectin translocation to the cell surface and reduced leukocyte recruitment in early phases of inflammation.

Animals↗

PubMed2001

The calcium inhibitor SR33805 reduces intimal formation following injury of the porcine carotid artery.

We studied the effect of SR33805, a calcium channel blocker, in vitro on the proliferation of vascular smooth muscle cells (SMC) stimulated by foetal calf serum, basic fibroblast growth factor and platelet derived growth factor, and in vivo with regard to SMC migration and proliferation which occurred following injury of the porcine carotid artery. The intimal lesion was induced by a silasten collar surgically positioned around the carotid artery and by a stenosis reducing blood flow by 50% for 30 days. Animals received SR33805 (5 mg/kg/day) 8 days before the induction of the lesion and up to 30 days after. In vitro, SR33805 inhibited in a dose-dependent manner growth factor-induced proliferation of SMC (0.20<IC(50)<0.46 microM). In vivo, SR33805 reduced the intima/media ratio of the cross sectional surface area (decrease of 60%, P<0.05) without affecting neointimal SMC density. The medial SMC density was 40% lower in treated than in control animals (upstream, P<0.05 and downstream to the stenosis, P<0.01). Thus, it appears that SR33805 significantly reduced intimal hyperplasia, which occurred after perivascular manipulation of the artery, an effect consistent with its in vitro proliferation inhibitory activity, suggesting that long-term treatment with SR33805 may reduce or delay SMC proliferation.

Animals↗

PubMed2001

Supra-aggregates.

Mixtures of oil (isooctane), water, and a double-chained ionic surfactant, Cu(AOT)2 [copper(II) bis(2-ethylhexyl)sulfosuccinate] form equilibrium phases consisting of spontaneous emulsions thermodynamically stable systems. The experimental conditions are such that the head polar group of the surfactant is totally hydrated. The emulsion droplets are comprised of supra aggregates, lamellar spherulites in which interior and exterior are bicontinuous microemulsions. The microstructures and component ratios can be predicted from elementary considerations that require only the notion of local and global packing constraints. The phenomenon of supra aggregation, microphases within any topologically closed container, in equilibrium with an external phase, appears quite general. The results throw some light on the meaning of 'phase' in mesostructured fluids.

Journal Article↗