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Biomedical subjects

M Brunet

Publications and source records attributed to M Brunet.

At least 19 recordsLinked to original sources
PubMed2006

The association between low physical fitness and high body mass index or waist circumference is increasing with age in children: the 'Québec en Forme' Project.

OBJECTIVE: To evaluate physical fitness and body composition of children involved in the 'Québec en Forme' (QEF) Project and to compare data obtained to the reference values of the 1981 Canada Fitness Survey (CFS). DESIGN: Cross-sectional study. SUBJECTS: A total of 1140 children (591 boys and 549 girls) of first (7 years), second (8 years) and fourth (10 years) grade from primary schools in the City of Trois-Rivières (Québec) were selected to participate in this study. MEASUREMENTS: Body mass index (BMI) and waist circumference (WC) were measured. The physical fitness tests included standing long jump, 1-min speed sit-ups and speed shuttle run. RESULTS: The prevalence of overweight in children ranged between 20 and 30%, which represents a substantial increase compared to the 1981 CFS. The relationship between BMI and WC was highly significant in boys and girls (r=0.90 and 0.86, respectively, P<0.0001). The negative correlations between BMI or WC and the performance in all physical fitness tests were mostly significant in children of both genders (-0.16 < or = r < or = -0.45, at least P<0.05), and these relationships were significantly greater in older children (P<0.05). Based on the 1981 CFS, only 4.7-14.1% of QEF boys still performed in the upper quartile of the distribution (fit boys), whereas 32.1-69% performed not much higher than the lower quartile (unfit boys) for each fitness test. In girls, the relative fitness decrease observed in 2003 was more pronounced since only 1-9.9% of subjects performed in the upper quartile of the distribution compared to 42.8-81.4% who did not perform higher than the lower quartile of the 1981 reference scores of the CFS. CONCLUSION: This study shows that BMI and WC are negatively correlated with physical fitness and that these associations are more pronounced in older children. Furthermore, physical fitness of our cohort, especially in girls, was much lower than what was documented in the 1981 CFS in subjects of the same age. This study thus emphasizes the necessity to develop early interventions to improve physical fitness in children and to prevent the increase of childhood obesity.

Body Composition↗
PubMed2006

Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy.

Stress or heat shock proteins (HSPs) are the most conserved proteins present in both prokaryotes and eukaryotes. Their expression is induced in response to a wide variety of physiological and environmental insults. These proteins play an essential role as molecular chaperones by assisting the correct folding of nascent and stress-accumulated misfolded proteins, and preventing their aggregation. HSPs have a dual function depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of HSPs. Several HSPs have also been demonstrated to directly interact with various components of the tightly regulated programmed cell death machinery, upstream and downstream of the mitochondrial events. On the other hand, extracellular located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response modulated either by the adaptive or innate immune system. This review will focus on HSP27, HSP70, and HSP90. We will discuss the dual role of these HSPs, protective vs. immunogenic properties, making a special emphasis in their utility as targets in cancer therapy.

Animals↗
PubMed2006

Mechanisms of cytochrome c release from mitochondria.

In healthy cells, cytochrome c (Cyt c) is located in the mitochondrial intermembrane/intercristae spaces, where it functions as an electron shuttle in the respiratory chain and interacts with cardiolipin (CL). Several proapoptotic stimuli induce the permeabilization of the outer membrane, facilitate the communication between intermembrane and intercristae spaces and promote the mobilization of Cyt c from CL, allowing for Cyt c release. In the cytosol, Cyt c mediates the allosteric activation of apoptosis-protease activating factor 1, which is required for the proteolytic maturation of caspase-9 and caspase-3. Activated caspases ultimately lead to apoptotic cell dismantling. Nevertheless, cytosolic Cyt c has been associated also to vital cell functions (i.e. differentiation), suggesting that its release not always occurs in an all-or-nothing fashion and that mitochondrial outer membrane permeabilization may not invariably lead to cell death. This review deals with the events involved in Cyt c release from mitochondria, with special attention to its regulation and final consequences.

Allosteric Regulation↗
PubMed2006

Multi-center evaluation of analytical performance of the microparticle enzyme immunoassay for sirolimus.

OBJECTIVES: This study evaluated the analytical characteristics of the new Abbott microparticle enzyme immunoassay (MEIA) for sirolimus. DESIGN AND METHODS: The protocol consisted of nine sections: evaluation of antibody specificity, linearity, detection limit, quantification limit, endogenous interferents, exogenous interferents, precision, proficiency testing panel, and method comparison. RESULTS: The mean analytical detection limit was 0.68 microg/L. The sirolimus concentration corresponding to a total CV of 20% was 1.5 microg/L. Linearity of response was demonstrated across the dynamic range of the assay. Total precision (CVs) at QC control levels from 5 to 22 microg/L ranged from 5.7 to 12.6%. Assay standardization was found to be in good agreement with LC/MS/MS as compared with target values for spiked sirolimus proficiency samples from an international sirolimus proficiency testing program. Good correlations (R values) of the immunoassay were observed in comparisons to LC/MS/MS. R values tended to be lower in comparisons with LC/UV methods. Across both LC-based methods and all study sites, there was approximately 25% overall positive slope bias due to cross reactivity of the MEIA antibody to metabolites of sirolimus. The assay cross-reactivity to metabolites of sirolimus parent drug ranged from 6 to 63%. Assay interferences were minimal with the exception of hematocrit, which presented a negative relationship to measured sirolimus concentration. CONCLUSIONS: The MEIA demonstrated acceptable analytical characteristics for use for routine monitoring of sirolimus immunosuppressive therapy, and is a viable alternative to HPLC-based methods for sirolimus monitoring.

Calibration↗
PubMed2006

Relationship between short sleeping hours and childhood overweight/obesity: results from the 'Québec en Forme' Project.

OBJECTIVE: To assess the relationship between short sleep duration and obesity-related variables in children involved in the 'Québec en Forme' Project. DESIGN: Cross-sectional study. SUBJECTS: A total of 422 children (211 boys and 211 girls) aged between 5 and 10 years from primary schools in the City of Trois-Rivières (Québec) were selected to participate in this study. MEASUREMENTS: Body weight, height and waist circumference were measured. The children were classified as normal, underweight, overweight or obese, according to body mass index (BMI) per age. An exhaustive questionnaire was administered by telephone to the parents of children. RESULTS: The percentage of overweight/obesity was 20.0% in boys and 24.0% in girls. When compared to children reporting 12-13 h of sleep per day, the adjusted odds ratio for childhood overweight/obesity was 1.42 (95% confidence interval 1.09-1.98) for those with 10.5-11.5 h of sleep and 3.45 (2.61-4.67) for those with 8-10 h of sleep after adjustment for age, sex, and other risk factors. Parental obesity, low parental educational level, low total family income, long hours of TV watching, playing videogames or computer utilization, absence of breastfeeding and physical inactivity were also significantly associated with childhood overweight/obesity. In addition, we observed a significant negative association adjusted for age between sleep duration and body weight (-0.33, P<0.01), BMI (-0.12, P<0.01) and waist circumference (-0.24, P<0.01) in boys. CONCLUSION: An inverse association was observed between sleep duration and the risk to develop childhood overweight/obesity. Longitudinal research will be required to confirm a potential link of causality between these variables.

Anthropometry↗
PubMed2006

Heat shock proteins: endogenous modulators of apoptotic cell death.

The highly conserved heat shock proteins (Hsps) accumulate in cells exposed to heat and a variety of other stressful stimuli. Hsps, that function mainly as molecular chaperones, allow cells to adapt to gradual changes in their environment and to survive in otherwise lethal conditions. The events of cell stress and cell death are linked and Hsps induced in response to stress appear to function at key regulatory points in the control of apoptosis. Hsps include anti-apoptotic and pro-apoptotic proteins that interact with a variety of cellular proteins involved in apoptosis. Their expression level can determine the fate of the cell in response to a death stimulus, and apoptosis-inhibitory Hsps, in particular Hsp27 and Hsp70, may participate in carcinogenesis. This review summarizes the apoptosis-regulatory function of Hsps.

Animals↗
PubMed2005

Giant-block twist grain boundary smectic phases.

Study of a diverse set of chiral smectic materials, each of which has twist grain boundary (TGB) phases over a broad temperature range and exhibits grid patterns in the Grandjean textures of the TGB helix, shows that these features arise from a common structure: "giant" smectic blocks of planar layers of thickness l(b) > 200 nm terminated by GBs that are sharp, mediating large angular jumps in layer orientation between blocks (60 degrees < Delta < 90 degrees ), and lubricating the thermal contraction of the smectic layers within the blocks. This phenomenology is well described by basic theoretical models applicable in the limit that the ratio of molecular tilt penetration length-to-layer coherence length is large, and featuring GBs in which smectic ordering is weak, approaching thin, melted (nematic-like) walls. In this limit the energy cost of change of the block size is small, leading to a wide variation of block dimension, depending on preparation conditions. The models also account for the temperature dependence of the TGB helix pitch.

Journal Article↗
PubMed2005

Pharmacokinetics of mycophenolate mofetil in kidney transplant patients with renal insufficiency.

Mycophenolate mofetil (MMF) is an immunosuppressant that is widely used for prophylaxis of rejection in solid organ transplantation. In this study, we examined the effect of renal insufficiency on the pharmacokinetics of MMF, particularly on the free fraction of drug in renal transplant patients. Our study was performed on 10 patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min), and 10 control patients with preserved renal function (CrCl >90 mL/min). All the patients had received a cadaveric donor graft at least 1 year prior and were clinically stable under treatment with MMF and cyclosporine. For each patient, we determined 12-hour areas under the curve (AUC(0-12 h)) for the metabolites: mycophenolic acid (MPA), 7-O-mycophenolic acid glucuronide (MPAG), and the free non-protein-bound fraction of MPA (f-MPA). The two groups were matched for age, sex, and MMF dose. Mean AUC(0-12 h) values for MPA were similar in both groups. The renal insufficiency group showed a significantly increased AUC(0-12 h) for MPAG (1550 +/- 392 vs 3527 +/- 1130 microg.h/mL, P < .001) and increased trough and AUC(0-12 h) values for f-MPA (0.023 +/- 0.02 vs 0.094 +/- 0.07 microg/mL, P = .003, and 0.87 +/- 0.3 vs 1.52 +/- 0.8 microg . h/mL, P = .016, respectively). We proposed that these differences should be taken into account when deciding upon the dose of this drug for the subset of patients with impaired transplant function.

Area Under Curve↗
PubMed2005

Steroids and living liver donation increase tacrolimus blood levels in living donor liver transplantation.

The aim of this study was to determine the tacrolimus blood levels in recipients of living donor liver transplants (LDLT) compared with recipients who undergo whole cadaveric liver grafts and to correlate the tacrolimus trough levels with the 12-hour area under the concentration (AUC) curve. From June 2002 to June 2003, the 10 LDLT were prospectively compared with 11 cadaveric transplants. The main immunosuppression was tacrolimus plus steroids. Intraoperative methylprednisolone was administered to all cadaveric organ recipients and only 6 of the 10 LDLT. Median tacrolimus trough levels at day 10 were 14.1 ng/mL for the LDLT group and 9.1 ng/mL for the CLT group (P = NS). The median tacrolimus AUC at day 10 were 185.2 ngxh/mL and 148.1 ngxh/mL for the LDLT group and the cadaveric group, respectively (P = NS). Median tacrolimus trough levels at day 2 were 24.3 ng/mL versus 9.9 ng/mL in the LDLT recipients with and without steroids, respectively (P < .05). Also, median tacrolimus AUC at day 2 were 239 ngxh/mL and 179.7 ngxh/mL when we compared LDLT recipients with and without steroids (P = NS). A significant correlation was observed between tacrolimus trough levels and AUC in the LDLT group (C.C. = 0.936; P < .0001). In conclusion, LDLT recipients display higher tacrolimus blood levels in comparison with cadaveric liver recipients, with a good correlation between tacrolimus trough levels and AUC. Intraoperative steroid administration induces higher tacrolimus levels in LDLT recipients.

Adrenal Cortex Hormones↗
PubMed2004

New concepts in cyclosporine pharmacokinetic and dynamic monitoring: the impact of concomitant immunosuppression on target C2 concentrations.

BACKGROUND: There is a correlation between cyclosporine (CsA) pharmacokinetics (PK) and pharmacodynamics (PD), especially 2 hours after drug administration. AIM: To evaluate the relationship between CsA PK and PD profiles in two groups of stable renal transplant patients treated with CsA alone or CsA plus mycophenolate mofetil (CsA+MMF), so as to define the best target for C2 and clarify the impact of concomitant immunosuppression. METHODS: Thirty-eight stable renal transplant recipients were treated with CsA (n=20) or CsA+MMF (n=18). Twelve nontreated normal healthy controls (NHC) were also included. Calcineurin activity (CNa), IL-2 production, and CsA levels were measured at 0 and 2 hours postdose. RESULTS: There were no significant differences in median CsA C2 values and CNa between the CsA alone and the CsA+MMF groups (388 microg/L and 497.5 microg/L and CNa 2h; 3.92% alkaline phosphatase [AP]; 3.94% AP, respectively). In vitro production of IL-2 was significantly lower in the CsA+MMF group than in the CsA group (median IL-2 2h: 280.52 ng/L, 169.48 ng/L, P<.001). The correlations (r) between C2 and CNa 2h were: CsA r=0.74; CsA+MMF r=0.84 (P<.001 in both cases). CONCLUSIONS: In stable renal transplant patients, median CsA C2 values below 500 microg/L were associated with inhibition of CNa and IL-2 synthesis. CNa and IL-2 production may be good biological markers of CsA immunosuppression. The measurement of CNa depends mainly on CsA concentration, whereas in vitro IL-2 production reflects the effect of both CsA and MMF. Further studies are necessary to define the optimal C2 target concentration and the possible impact of concomitant immunosuppression.

Calcineurin Inhibitors↗
PubMed2003

Structure and texture of anisotropic nematic gels.

Anisotropic nematic gels are prepared via in situ polymerization of diacrylate monomers in an oriented nematic liquid crystal (LC) matrix. The structure of the gels is studied from micrometer to nanometer scales by optical microscopy, small angle neutron scattering, and theta/2theta light scattering. A strong anisotropy is evidenced at all scales without electric field for both mesogenic and nonmesogenic monomers. The gel network can be pictured as an ordered but strongly distorted and polydisperse structure with two characteristic sizes: the mean size of the polymer objects and a correlation length between these objects, corresponding to the mean-size of the LC domains, which are estimated from neutron and light scattering results to be of the order of some tens of nanometers and some micrometers, respectively. Moreover, a sheet-like structure of the polymer network is evidenced. When an electric field is applied, one part of the LC switches while the other part remains anchored to the polymer network. The electric field dependence of the volume fraction of anchored LC is estimated from the analysis of the light scattering data. We emphasize systematic correlations between structure and electro-optical properties of the gels.

Anisotropy↗
PubMed2003

Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C(2).

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p<0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Area Under Curve↗
PubMed2002

High frequency of a 30-bp deletion of Epstein-Barr virus latent membrane protein 1 gene in primary HIV non-Hodgkin's brain lymphomas.

A characteristic 30-base pair (bp) deletion (del) in the 3' end of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene, coding for the C-terminal NF-kappa B activation domain, has been identified in various lymphoproliferative disorders and nasopharyngeal carcinomas. In the single report to date of human immunodeficiency virus primary brain lymphomas (HIV-PBLs), del-LMP1 was noted in seven cases out of nine. The present study was designed to identify this deletion in a series of 31 diffuse large B-cell HIV-PBLs, with the aim of determining its possible oncogenic action. The presence of EBV was confirmed by EBER mRNA in situ hybridization. After genomic extraction from frozen tissue, two 20-base oligonucleotide primers flanking the site of the 30-bp deletion were used. DNA sequencing of the polymerase chain reaction (PCR) products confirmed an identical segment spanning 30-bp and 69-bp, frequently associated with mutational hotspots in 19 cases (61%). A role for del-LMP1 in the oncogenic potential of EBV in systemic proliferations is a matter of debate. Its high incidence suggests that the oncogenic mechanism of LMP1 in the brain might differ significantly from that in systemic lymphoid proliferations, and might be enhanced by HIV infection.

Adult↗
PubMed2001

Mycophenolic acid plasma concentrations: influence of comedication.

Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p < 0.0001). According to the post transplant period (1-3, 4-6 and >6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.

Adult↗
PubMed2000

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Adolescent↗
PubMed2000

Switching behavior and electro-optical properties of liquid crystals in nematic gels

Anisotropic nematic gels are prepared via in situ polymerization of diacrylate monomers in an orientated nematic liquid crystal (LC) matrix. The switching behavior of the LC molecules under electric field is probed in polarized Raman spectroscopy and straight theta-2straight theta elastic light scattering experiments. The electro-optical characteristics of the gels are directly related to the electric field dependence of the fraction of switched molecules. The electro-optical contrast relates to the coexistence of switched LC domains and LC domains anchored to the polymer network.

Journal Article↗
PubMed2000

Reference change value for HbA1c in patients with type 2 diabetes mellitus.

We estimated reference change value and steady state disease biological variation of glycohemoglobin (HbA1c) from serial measurements in 47 clinically stable type 2 diabetes patients whose home-measured capillary glucose was stable throughout the study. Whole blood HbA1c assays were performed by turbidimetric inhibition immunoassay. The analytical imprecision (coefficient of variation) was 7.1% and 5.0% for control materials with HbA1c of 5.1% and 10.7%, respectively (n=152). The sampling interval was 6 months. Patients were classified into three groups (good, acceptable and poor control) according to the American Diabetes Association (ADA) clinical practice recommendations of 1999 based on HbA1c reference interval. Steady state disease biological variation for each control group was 7.9%, 5.4% and 3.9%. HbA1c absolute reference change value was 1.42, 1.50 and 1.37%, or as relative reference change value, 29.1%, 24.4% and 17.8%, respectively. The analytical goal, defined as one-half of the biological variation, was lower than 3.9% for well-controlled patients.

Aged↗