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Biomedical subjects

S Bernard

Publications and source records attributed to S Bernard.

At least 19 recordsLinked to original sources
PubMed2006

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism.

AIMS/HYPOTHESIS: Adiponectin is upregulated during adipogenesis and downregulated in insulin-resistant states. The mechanism(s) governing the re-arrangements from adipogenesis to facilitated lipolysis during pregnancy are unknown. Our purpose was to analyse the role of adiponectin relative to the metabolic changes in human pregnancy. SUBJECTS, MATERIALS AND METHODS: Lean women (BMI <25 kg/m(2)) were evaluated longitudinally before conception, and in early (12-14 weeks) and late (34-36 weeks) pregnancy. Insulin sensitivity was measured using the glucose clamp technique. Venous blood and subcutaneous adipose tissue biopsies were obtained at each time point. RESULTS: Adiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9+/-1.4 vs 13.5+/-1.8 microg/ml). The hypoadiponectinaemia was reflected by a 2.5-fold decrease in white adipose tissue adiponectin mRNA. These changes were associated with a 25% increase in fat mass (23.7+/-2.9 vs 18.9+/-2.9 kg). Insulin infusion decreased high molecular weight adiponectin complexes in pregravid women (9.9+/-0.6 vs 6.2+/-0.06) and the suppressive effect of insulin was lost during pregnancy. The pregnancy-mediated changes in adiponectin were strongly correlated with basal insulin levels and insulin sensitivity (p<0.0001). The relationship between adiponectin and insulin sensitivity was related to the decreased insulin regulation of glucose utilisation (r=0.55, p<0.001) but not of endogenous hepatic glucose production. CONCLUSIONS/INTERPRETATION: These data demonstrate that pregnancy is associated with adiponectin changes in lean women. Hypoadiponectinaemia is reflected by a lower amount of high molecular weight adiponectin and by the ratio of high to low molecular weight multimers. The adiponectin changes relate to decreased insulin sensitivity of glucose disposal rather than alterations of lipid metabolism.

Adiponectin↗
PubMed2005

Dosimetric study of a new polymer encapsulated palladium-103 seed.

The use of low-energy photon emitters for brachytherapy applications, as in the treatment of prostate or ocular tumours, has increased significantly over the last few years. Several new seed models utilizing 103Pd and 125I have recently been introduced. Following the TG43U1 recommendations of the AAPM (American Association of Physicists in Medicine) (Rivard et al 2004 Med. Phys. 31 633), dose distributions around these low-energy photon emitters are characterized by the dose rate constant, the radial dose function and the anisotropy function in water. These functions and constants can be measured for each new seed in a solid phantom (i.e. solid water such as WT1) using high spatial resolution detectors such as very small thermoluminescent detectors. These experimental results in solid water must then be converted into liquid water by using Monte Carlo simulations. This paper presents the dosimetric parameters of a new palladium seed, OptiSeed (produced by International Brachytherapy (IBt), Seneffe, Belgium), made with a biocompatible polymeric shell and with a design that differs from the hollow titanium encapsulated seed, InterSource103, produced by the same company. A polymer encapsulation was chosen by the company IBt in order to reduce the quantity of radioactive material needed for a given dose rate, and to improve the symmetry of the radiation field around the seed. The necessary experimental data were obtained by measurements with LiF thermoluminescent dosimeters (1 mm3) in a solid water phantom (WT1) and then converted to values in liquid water using Monte Carlo calculations (MCNP-4C). Comparison of the results with a previous study by Reniers et al (2002 Appl. Radiat. Isot. 57 805) shows very good agreement for the dose rate constant and for the radial dose function. In addition, the results also indicate an improvement in isotropy compared to a conventional titanium encapsulated seed. The relative dose (anisotropy value relative to 90 degrees ) from the seed at a distance of 3 cm is close to 70% at 0 degrees whereas that for the titanium encapsulated InterSource103seed is close to 40%. This paper also presents some new Monte Carlo calculations relating to shadowing produced by the seeds in an array implanted for a prostate cancer treatment. Recently, Mobit and Badragan (2004 Phys. Med. Biol. 49 3171) reported shadowing resulting in a 10% decrease in dose from titanium encapsulated 125I seed. We used Monte Carlo simulations (MCNP-4C) to evaluate shadowing for the InterSource103 titanium encapsulated seed and the OptiSeed polymer encapsulated seed. For a specific geometry specified, dose decreases of 13% and 7% were found for the InterSource103 titanium encapsulated and the OptiSeed polymer encapsulated seed, respectively.

Brachytherapy↗
PubMed2005

tBid interaction with cardiolipin primarily orchestrates mitochondrial dysfunctions and subsequently activates Bax and Bak.

TNFR1/Fas engagement results in the cleavage of cytosolic Bid to truncated Bid (tBid), which translocates to mitochondria. We demonstrate that recombinant tBid induces in vitro immediate destabilization of the mitochondrial bioenergetic homeostasis. These alterations result in mild uncoupling of mitochondrial state-4 respiration, associated with an inhibition the adenosine diphosphate (ADP)-stimulated respiration and phosphorylation rate. tBid disruption of mitochondrial homeostasis was inhibited in mitochondria overexpressing Bcl-2 and Bcl-XL. The inhibition of state-3 respiration is mediated by the reorganization of cardiolipin within the mitochondrial membranes, which indirectly affects the activity of the ADP/ATP translocator. Cardiolipin-deficient yeast mitochondria did not exhibit any respiratory inhibition by tBid, proving the absolute requirement for cardiolipin for tBid binding and activity. In contrast, the wild-type yeast mitochondria underwent a similar inhibition of ADP-stimulated respiration associated with reduced ATP synthesis. These events suggest that mitochondrial lipids rather than proteins are the key determinants of tBid-induced destabilization of mitochondrial bioenergetics.

Adenosine Diphosphate↗
PubMed2003

Epidemiology and prevention of unexpected in-hospital deaths.

INTRODUCTION: The medical literature has only documented the importace of adverse events in terms of patient outcomes and cost to the health service over the last decade. This review focuses on the incidence, risk factors and prevention on unexpected in-hospital deaths. DISCUSSION: The incidence of unexpected in-hospital deaths in the two major retrospective studies was 0.5% and 0.8% of all hospital admissions. A prospective study of surgical patients documented an incidence of nearly 7.1%. The risk factors that have been associated with hospital death include: increasing age; non-elective operative procedure; negligence; human error and unstable bedside observations in the hours prior to death. Although a number of intreventions have been suggested to prevent unexpected in-hospital deaths, very few studies have been performed to determine effectiveness. In a single institution historical control study, the introduction of a Medical Emergency Team was associated with 50% reduction in the casemix adjusted incidence of in-hospital cardiac arrest calls. CONCLUSION: There are a number of studies to suggest that in-hospital deaths are both predictable and preventable. More work is required to determine effective strategies to manage this problem.

Hospital Mortality↗
PubMed2002

Parallel-in-time molecular-dynamics simulations.

While there have been many progress in the field of multiscale simulations in the space domain, in particular, due to efficient parallelization techniques, much less is known in the way to perform similar approaches in the time domain. In this paper we show on two examples that, provided we can describe in a rough but still accurate way the system under consideration, it is indeed possible to parallelize molecular dynamics simulations in time by using the recently introduced pararealalgorithm. The technique is most useful for ab initio simulations.

Journal Article↗
PubMed2002

An update of the Courtot x Chinese Spring intervarietal molecular marker linkage map for the QTL detection of agronomic traits in wheat.

We made an update of the intervarietal molecular marker linkage map of the wheat genome developed using a doubled-haploid (DH) population derived from the cross between the cultivars "Courtot" and "Chinese Spring". This map was constructed using 187 DH lines and 659 markers. The genome was well covered (more than 95%) except for chromosomes from homoeologous group 4 and chromosomes 5D and 7D, which had gaps slightly larger than 50 cM. A core-map based on a set of 200 anchor loci (one marker each 18.4 cM) was developed. The total length of this map was 3,685 cM which is similar to the size of the international reference map of the ITMI population (3,551 cM). Map coverage was identical for the three genomes (A, B and D) and for the number of anchor loci, as well as for the size of the map. Using this map, QTLs for several agronomic traits were detected on phenotypic data from the population grown in Clermont-Ferrand (France) under natural field conditions over 6 years, and in Norwich (UK) in controlled conditions and under natural field conditions in 1 year. Almost all of the 21 chromosomes were involved in at least one trait. However, several regions seemed to contain gene clusters either for grain traits (and thus bread-making quality) or plant development traits.

Chromosome Mapping↗
PubMed2002

Study of Langmuir-Blodgett phospholipidic films deposited on surface enhanced Raman scattering active gold nanoparticle monolayers.

Surface enhanced Raman scattering (SERS) was used to study phospholipid monolayers transferred by the Langmuir-Blodgett (LB) technique to SERS active substrates. These substrates, which were constituted of gold colloidal nanoparticles bound to polysilane films grafted onto glass plates, showed a uniform and homogeneous layer with strong interacting particles as revealed from UV-visible extinction spectra and atomic force microscopy images. Laser excitation at 632.8 nm within the red part of the localized surface plasmon resonance leads to intense and reproducible SERS spectra of trans-1,2-bis(4-pyridyl)ethylene (BPE). From SERS measurements at different pHs it was possible to determine the apparent pK(a) of BPE adsorbed on gold-coated silanized substrates in the absence and presence of one LB monomolecular layer of phospholipids. These SERS titrations allowed the estimation of the pH at the metal-LB film interface.

Gold↗
PubMed2002

Impact of adding 5.5 mM glucose to SOF medium on the development, metabolism and quality of in vitro produced bovine embryos from the morula to the blastocyst stage.

Although toxic for early stages of embryo development, glucose is a physiological metabolic substrate at the morula and blastocyst stages. We evaluated the effect of adding 5.5 mM glucose from the morula stage on bovine blastocyst development and quality. In vitro matured and fertilised bovine oocytes were cultured in modified Synthetic Oviduct Fluid medium containing 5% fetal calf serum, but without added glucose, up to day 5 post-insemination (pi). Morulae were selected and further cultured in the presence or absence of 5.5 mM glucose. Blastocyst and hatched blastocyst rates were recorded. Oxygen, glucose and pyruvate uptakes as well as lactate release were evaluated. The quality of the resulting blastocysts was evaluated by the cell allocation to the inner cell mass (ICM) and trophectoderm (TE) and by the apoptotic index. Adding glucose increased the blastocyst rate at day 8 pi (80% vs 65%) but had no impact on hatching rate (25% vs 28%). A 22% decrease in oxygen uptake was observed in the presence of glucose, concomitant with an increase in lactate release, although no change was observed in pyruvate uptake. A slight decrease in blastocyst cell number was observed at day 7 in the presence of glucose while neither the ICM/TE cell ratio nor the apoptotic index were affected. In conclusion, adding 5.5 mM glucose from the morula stage has a limited impact on blastocyst rate and quality although important modifications were observed in embryo metabolism. It remains to be determined whether those modifications could influence embryo viability after transfer.

Animals↗
PubMed2002

Pharmacokinetics of marbofloxacin in horses.

Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the terminal half-life 756 +/- 1.99 h. The marbofloxacin absolute bioavailabilities after subcutaneous and oral administration were 98 +/- 11% and 62 +/- 8%, respectively. The MIC required to inhibit 90% of isolates (MIC90) was 0.027 microg/ml for enterobacteriaceae and 0.21 microg/ml for Staphylococcus aureus. The values of surrogate markers of antimicrobial efficacy (AUIC, Cmax/MIC ratio, time above MIC90) were calculated and the marbofloxacin concentration profiles simulated for repeated administrations. These data were used to determine rational dosage regimens for target bacteria. Considering the breakpoint values of efficacy indices for fluoroquinolones, a marbofloxacin dosage regimen of 2 mg/kg bwt/24 h by i.v., subcutaneous or oral routes was more appropriate for enterobacteriaceae than for S. aureus.

Administration, Oral↗
PubMed2001

Radioisotopic imaging allows optimization of adenovirus lung deposition for cystic fibrosis gene therapy.

Cystic fibrosis is a common, heriditary disease resulting from mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Airway transfer of the CFTR gene is a potential strategy to treat or prevent the lung pathology that is the main cause of morbidity and mortality. Among the vectors used for gene therapy, adenoviruses have shown their ability to transfer the CFTR gene to respiratory epithelial cells, using either instillation or nebulization. Our objective was to characterize the lung deposition of aerosolized adenovirus by quantitative radioisotopic imaging, the only noninvasive technique allowing in vivo quantitation of inhaled drugs. We first labeled an adenovirus expressing human CFTR with the gamma-emitting radioisotope, technetium 99m (99mTc), and determined the best labeling conditions to allow preservation of virus bioactivity. We then administered the radioaerosol to baboons, determined lung regional deposition of 99mTc-labeled adenovirus, and compared the expression of CFTR transcripts 3 and 21 days after inhalation. The expression of vector-encoded mRNA ranged from 4 to 22% with respect to the endogenous CFTR mRNA depending on the lung segments. Moreover, we have developed a model using 99mTc-DTPA (diethylenetriamine pentaacetic acid), which can be used, as an alternative to adenovirus, to determine the profile of lung deposition of the vector. This study demonstrates that scintigraphy is a useful technique to achieve optimization of gene administration to the airways.

Adenoviridae↗
PubMed2001

Predicted mercury concentrations in hair from infant immunizations: cause for concern.

Mercury (Hg) is considered one of the worlds most toxic metals. Current thinking suggests that exposure to mercury occurs primarily from seafood contamination and rare catastrophic events. Recently, another common source of exposure has been identified. Thimerosal (TMS), a preservative found in many infant vaccines, contains 49.6% ethyl mercury (EtHg) by weight and typically contributes 25 microg of EtHg per dose of infant vaccine. As part of an ongoing review, the Food and Drug Administration (FDA) announced in 1999 that infants who received multiple TMS-preserved vaccines may have been exposed to cumulative Hg in excess of Federal safety guidelines. According to the centers for disease control (CDC) recommended immunization schedule, infants may have been exposed to 12.5 microg Hg at birth, 62.5 microg EtHg at 2 months, 50 microg EtHg at 4 months, 62.5 microg EtHg at 6 months, and 50 microg EtHg at approximately 18 months, for a total of 237.5 microg EtHg during the first 18 months of life, if all TMS-containing vaccines were administered. Neurobehavioral alterations, especially to the more susceptible fetus and infant, are known to occur after relatively low dose exposures to organic mercury compounds. In effort, to further elucidate the levels of ethyl mercury resulting from exposure to vaccinal TMS, we estimated hair Hg concentrations expected to result from the recommended CDC schedule utilizing a one compartment pharmacokinetic model. This model was developed to predict hair concentrations from acute exposure to methymercury (MeHg) in fish. Modeled hair Hg concentrations in infants exposed to vaccinal TMS are in excess of the Environmental Protection Agency (EPA) safety guidelines of 1 ppm for up to 365 days, with several peak concentrations within this period. More sensitive individuals and those with additional sources of exposure would have higher Hg concentrations. Given that exposure to low levels of mercury during critical stages of development has been associated with neurological disorders in children, including ADD, learning difficulties, and speech delays, the predicted hair Hg concentration resulting from childhood immunizations is cause for concern. Based on these findings, the impact which vaccinal mercury has had on the health of American children warrants further investigation.

Forecasting↗
PubMed2001

Cytokine gene expression in lymph node and spleen of sheep in response to Salmonella infection by two serotypes displaying different host specificity.

In order to investigate the determinism of the host specificity and to better understand the host resistance mechanisms, infections of sheep were performed with either S. abortusovis, serotype specific for ovine species, or with S. dublin, serotype adapted to cattle and accidentally transmissible to human. Following a subcutaneous challenge, S. dublin disseminated more rapidly towards lymphoid tissues than S. abortusovis. However, S. abortusovis tended to persist in spleen more efficiently than S. dublin. Using a quantitative RT-PCR method, the expression level of ovine cytokines genes was measured in the draining lymph node and in the spleen, in the course of infection. Inflammatory cytokine response was characterised by an early and strong increase of IL-1beta and TNFalpha mRNA in both lymphoid organs following S. dublin infection, while S. abortusovis challenge only induced IL-1beta mRNA increase in the spleen at day 3 post-inoculation. Likewise, S. dublin infection provoked a marked increase of IL-12 mRNA and a slight up-regulation of IFNgamma gene transcription in the local lymphoid site, in contrast to S. abortusovis infection. Elsewhere, both serotypes induced a strong and early IL-10 mRNA production and had no effect on IL-4 gene expression. Finally, taken together, these data suggest that the intensity of inflammatory and anti-infectious cytokine responses, but not the type 2 cytokine response, is serotype-dependent. They also suggest that the host-specific serotype, by limiting the host cytokine-mediated defence, could favour its persistence within lymphoid organs.

Animals↗