A diagenetic control on the Early Triassic Smithian-Spathian carbon isotopic excursions recorded in the marine settings of the Thaynes Group (Utah, USA).

In the aftermath of the end-Permian mass extinction, Early Triassic sediments record some of the largest Phanerozoic carbon isotopic excursions. Among them, a global Smithian-negative carbonate carbon isotope excursion has been identified, followed by an abrupt increase across the Smithian-Spathian boundary (SSB; ~250.8 Myr ago). This chemostratigraphic evolution is associated with palaeontological evidence that indicate a major collapse of terrestrial and marine ecosystems during the Late Smithian. It is commonly assumed that Smithian and Spathian isotopic variations are intimately linked to major perturbations in the exogenic carbon reservoir. We present paired carbon isotopes measurements from the Thaynes Group (Utah, USA) to evaluate the extent to which the Early Triassic isotopic perturbations reflect changes in the exogenic carbon cycle. The δ(13) Ccarb variations obtained here reproduce the known Smithian δ(13) Ccarb -negative excursion. However, the δ(13) C signal of the bulk organic matter is invariant across the SSB and variations in the δ(34) S signal of sedimentary sulphides are interpreted here to reflect the intensity of sediment remobilization. We argue that Middle to Late Smithian δ(13) Ccarb signal in the shallow marine environments of the Thaynes Group does not reflect secular evolution of the exogenic carbon cycle but rather physicochemical conditions at the sediment-water interface leading to authigenic carbonate formation during early diagenetic processes.

In vivo exposure of marine mussels to carbamazepine and 10-hydroxy-10,11-dihydro-carbamazepine: Bioconcentration and metabolization.

Aquatic organisms are exposed to pharmaceuticals present in natural waters, but few data are available on the accumulation of these substances in such organisms. The present study evaluated the in vivo bioconcentration of two anticonvulsants--carbamazepine (CBZ) and 10-hydroxy-10,11-dihydro-carbamazepine (10 OH)--in marine mussels (Mytilus galloprovincialis) exposed to nominal 10 µg L(-1) concentrations for one week. The bioconcentration factors (BCFs) were 3.9 and 4.5 L kg(-1) dry weight (dw) for CBZ and 10 OH, respectively. CBZ accumulation reached an average tissue concentration of 29.3 ± 4.8 ng g(-1) dw, and 10 OH accumulated up to 40.9 ± 4.6 ng g(-1) dw in tissues within one week, showing first-order kinetics. BCF obtained with linear QSAR models correctly estimated the CBZ bioconcentration and overestimated the 10 OH bioconcentration to some extent. The detection of two metabolites (carbamazepine-10,11-epoxide and acridine) among the five sought suggested an active metabolism for CBZ. In contrast, none of the 10 OH metabolites were detected in mussels exposed to 10 OH. CBZ showed higher accumulation in the digestive gland, where some relevant metabolites were detected, than in other studied tissues. The implication of those findings on field biomonitoring is discussed.

Immune signalling responses in intestinal epithelial cells exposed to pathogenic Escherichia coli and lactic acid-producing probiotics.

Enterohaemorrhagic Escherichia coli O157:H7 and adherent-invasive Escherichia coli are two groups of enteric bacterial pathogens associated with haemorrhagic colitis and Crohn's Disease, respectively. Bacterial contact with host epithelial cells stimulates an immediate innate immune response designed to combat infection. In this study, immune responses of human epithelial cells to pathogens, either alone or in combination with probiotic bacteria were studied. Industrially prepared Lactobacillus helveticus strain R0052 was first examined by microarray analysis and then compared to broth-grown strains of R0052 and Lactobacillus rhamnosus strain GG using quantitative realt-time polymerase chain reaction. Results showed host immune activation responses increased following pathogen exposure, which were differentially ameliorated using probiotics depending on both the preparation of probiotics employed and conditions of exposure. These findings provide additional support for the concept that specific probiotic strains serve as a promising option for use in preventing the risk of enteric bacterial infections.

Transcriptomic response of immune signalling pathways in intestinal epithelial cells exposed to lipopolysaccharides, Gram-negative bacteria or potentially probiotic microbes.

In order to understand the appropriate use of potentially probiotic Gram-positive microbes through their introduction in the gut microbiome, it is necessary to understand the influence of individual bacteria on the host-response system at a cellular level. In the present study, we have shown that lipopolysaccharides, flagellated Gram-negative bacteria, potentially probiotic Gram-positive bacteria and yeast interact differently with human intestinal epithelial cells with a custom-designed expression microarray evaluating 17 specific host-response pathways. Only lipopolysaccharides and flagellated Gram-negative bacteria induced inflammatory response, while a subset of Gram-positive microbes had anti-inflammatory potential. The main outcome from the study was the differential regulation of the central mitogen-activated protein kinase signalling pathway by these Gram-positive microbes versus commensal/pathogenic Gram-negative bacteria. The microarray was efficient to highlight the impact of individual bacteria on the response of intestinal epithelial cells, but quantitative real-time polymerase chain reaction validation demonstrated some underestimation for down-regulated genes by the microarray. This immune array will allow us to better understand the mechanisms underlying microbe-induced host immune responses.

Methotrexate pharmacokinetics in childhood acute lymphoblastic leukaemia: a prognostic value?

WHAT IS KNOWN AND OBJECTIVE: In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL. METHODS: Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (V(d) ) of the drug were estimated by the NONMEM computer program and also compared between both groups. RESULTS AND DISCUSSION: Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse. WHAT IS NEW AND CONCLUSION: Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

[Continuous epidural block versus continuous psoas compartment block for postoperative analgesia after major hip or femoral surgery in children: a prospective comparative randomized study]. / Analgésie péridurale continue versus bloc continu du compartiment psoas pour l'analgésie postopératoire après chirurgie majeure du bassin ou du fémur chez l'enfant : étude prospective comparative randomisée.

BACKGROUND: Intravenous opioids and/or continuous epidural block (CEB) are used for postoperative analgesia after hip and/or femoral shaft surgery but adverse effects limit their use in children. A continuous psoas compartment block (CPCB), effective technique in adults can be an alternative. In this randomized comparative study, we wanted to evaluate CEB and CPCB in children after major hip surgery in terms of adverse events, pain relief and ropivacaine plasma concentrations. METHODS: After ethical committee and parents' approval, 40 children scheduled for hip surgery were included and randomly allocated to receive CPCB or CEB. After general anaesthesia induction, 0.5 mL/kg of 0.375% ropivacaine were injected via the epidural or lumbar plexus catheter. After surgery, 0.1 ml/kg per hour (group CPCB) or 0.2 ml/kg per hour (group CEB) of 0.2% ropivacaine was infused for 48h. Post-operative pain was evaluated using VAS or CHIPPS scores values at h1, h6, h12, h18, h24, h36 and h48, as well as doses of first line (paracetamol 15 mg/kg/6h) or second line rescue analgesia (0.2mg/kg intravenous nalbuphine), if pain score remained high after 30 mm. niflumic acid was systematically used. Adverse events were noted as well as parents' satisfaction at 48h. Ropivacaine plasma concentrations were measured four times up to 48h (h1, h6, h24 and h48) by high performance gas chromatography. RESULTS: Forty children 1 to 12 years old (CPCB=20, CEB=20) were included. The demographic data were equivalent in both groups. Postoperative analgesia was excellent for both continuous block techniques during the whole studied period. Doses of rescue analgesics were comparable in both groups at the end of the 48h. Number of children who had at least one side effect is significantly higher in CEB group. Furthermore, the number of local anaesthetic premature stops was significantly more frequent in this group. Median values of ropivacaine plasma level in CEB group were significantly higher than CPCB group at h6 and h24. Ten parents in the CEB group and 15 in CPCB group were satisfied. CONCLUSION: Continuous psoas compartment block is an effective technique of postoperative analgesia after major hip or femoral surgery in children. It equally manages postoperative pain with significantly less adverse event and decreased ropivacaine doses and plasma concentration than CEB.

Characterization of swine adiponectin and adiponectin receptor polymorphisms and their association with reproductive traits.

In this study, polymorphisms in genes encoding porcine adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) were evaluated for associations with reproductive traits in a Landrace sow population. Sixteen SNPs were identified, and among these, associations were found between reproductive traits and five SNPs. Heterozygous multiparous females for SNP ADIPOQEF601160:c.178G>A had fewer stillborn piglets (P < 0.05) and shorter weaning-to-oestrus intervals (P < 0.05). Multiparous females bearing the mutant allele for SNP ADIPOQEF601160:c.*1094_1095insC gave birth to fewer stillborn piglets (P < 0.05). In addition, selection for the ADIPOQ [A;C] haplotype is expected to result in multiparous sows having the lowest number of stillborn piglets and shorter weaning-to-oestrus intervals. In second-parity sows, the polymorphism in ADIPOR1 (AY856513:c.*129A>C) showed significant associations with live-born (P < 0.01) and stillborn (P < 0.05) piglets. In multiparous sows, a significant association was observed for an ADIPOR2 polymorphism (AY856514:c.*112G>A), with the c.*112GA genotype associated with shorter weaning-to-oestrus intervals (P < 0.01). Haplotype analyses of ADIPOR2 SNPs revealed that selection in favour of the [A;C] haplotype and against the [G;G] haplotype may result in sows having an increased number of live-born piglets and shorter weaning-to-oestrus intervals. We have therefore described specific SNPs and haplotypes that are associated with large litter size, fewer stillborn and mummified piglets and shorter weaning-to-oestrus intervals. Selection for these SNPs and haplotypes is a strategy to improve reproductive success in pigs.

Quantifying the contribution of nitrification and denitrification to the nitrous oxide flux using 15N tracers.

Microbial transformations of nitrification and denitrification are the main sources of nitrous oxide (N2O) from soils. Relative contributions of both processes to N2O emissions were estimated on an agricultural soil using 15N isotope tracers (15NH4+ or 15NO3-), for a 10-day batch experiment. Under unsaturated and saturated conditions, both processes were significantly involved in N2O production. Under unsaturated conditions, 60% of N-N2O came from nitrification, while denitrification contributed around 85-90% under saturated conditions. Estimated nitrification rates were not significantly different whatever the soil moisture content, whereas the proportion of nitrified N emitted as N2O changed from 0.13 to 2.32%. In coherence with previous studies, we interpreted this high value as resulting from the decrease in O2 availability through the increase in soil moisture content. It thus appears that, under limiting aeration conditions, some values for N2O emissions through nitrification could be underestimated.

[Renal cancer: what can we expect from emerging new technologies: radiofrequency and cryoablation?]. / Cancer du rein. Qu'attendre des nouvelles technologies: radiofréquence et cryoablation?

Radiofrequency and cryoablation are both minimally invasive techniques applied to the treatment of renal cell carcinoma. These techniques allow in situ destruction of neoplasm. Although cryotherapy is the most studied, radiofrequency is the most currently used technique. Indications mostly accepted as elective indication are the less than 4 cm in diameter exophytic tumors. Radiofrequency and cryoablation can also be proposed in patients with solitary kidney, multiple bilateral tumors and patients with contraindication for surgical resection. The radiofrequency parietal tract can be coagulated at the time of radiofrequency electrode withdrawal reducing the rare risk of parietal tumor dissemination. Preliminary oncological results in exophytic small renal tumors are promising with only few complications. A longer follow-up is however mandatory to better define the place of these two new technologies in the treatment of renal cancer.

[Risks associated with MRI: safety rules, incidents, and accidents]. / Risque IRM: règles de sécurité, incidents et accidents.

It is now accepted that MR imaging does not present any biological risk for humans, even in cases of repeated exposure. However, several of the MR components (magnetic field, gradients, RF pulses, electrodes...) may cause some inconveniences to patients, most of them being reversible. However, severe accidents have been reported. Even though screening of patients for MR imaging eligibility is performed to identify patients with contra-indications to MRI, the lack of vigilance or the ignorance of certain basic safety requirements could lead to serious adverse effects, including death. The goal of this article is to review the various accidents reported with MRI, to explain their mechanism, and to describe means of prevention.

Control of electroosmotic flow in zirconia-coated capillaries.

The inner surface of a silica capillary has been modified using an anhydrous sol-gel method: zirconium propoxide reacted with silanol groups to give, after hydrolysis, a "zirconia-like" surface. The electroosmotic properties of zirconia-modified capillaries have been studied under various conditions: working parameters were nature and concentration of the electrolyte, ionic strength, pH and solvent composition. Using different ions such as sodium, potassium, chloride, nitrate or methanoate, a positive electroosmotic flow (cathodic flow) was observed in the pH range 5-11. But below pH 5, a negative electroosmotic flow (anodic flow) occurred, corresponding to a permanent positive surface charge of the capillary walls. The value of the electroosmotic flow (including the sign) can be easily controlled by adding multivalent ions in the electrolyte. Some of these modifications of surface charge can be made irreversible. The observed electroosmotic flow has been related to surface characteristics using the triple layer model. With the large set of working parameters, the optimisation of separations can be facilitated. An example of flow control is given for the separation of four antihistaminic compounds.

Analysis of 5S rDNA arrays in Arabidopsis thaliana: physical mapping and chromosome-specific polymorphisms.

A physical map of a pericentromeric region of chromosome 5 containing a 5S rDNA locus and spanning approximately 1000 kb was established using the CIC YAC clones. Three 5S rDNA arrays were resolved in this YAC contig by PFGE analysis and we have mapped different types of sequences between these three blocks. 5S rDNA units from each of these three arrays of chromosome 5, and from chromosomes 3 and 4, were isolated by PCR. A total of 38 new DNA sequences were obtained. Two types of 5S rDNA repeated units exist: the major variant with 0.5-kb repeats and one with short repeats (251 bp) only detected on YAC 11A3 from chromosome 3. Although the 38 sequences displayed noticeable heterogeneity, we were able to group them according to their 5S array origin. The presence of 5S array-specific variants was confirmed with the restriction polymorphism study of all the YACs carrying 5S units.

Influences of endurance training on the ultrastructural composition of the different muscle fiber types in humans.

To investigate changes in the ultrastructure of the different muscle fiber types induced by endurance training ten sedentary subjects (five women and five men) were exercised on bicycle ergometers 5 times a week for 30 min. After 6 weeks of training there were significant changes in VO2max (+14%), in the percentage of type I (+12%) and type IIB fibers (-24%) as well as in the volume densities of mitochondria. The latter increased 35% in type I, 55% in type IIA and 35% in type IIB fibers. The relative increase in subsarcolemmal mitochondria was larger than in interfibrillar mitochondria in all fiber types. There was also a significant increase in the volume density of intracellular lipid in type II fibres. It is concluded that high intensity endurance training leads to an enhancement of the oxidative capacity in all muscle fiber types.

Scaling mitochondrial volume in heart to body mass.

The heart mass was measured and the volume density of mitochondria, VV(mt,f), morphometrically estimated in 11 mammalian species ranging from shrew (3 g) to cattle (920 kg). The mass or the volume of the heart muscle (Vh) was found to scale as Mb0 .970 whereas VV(mt,f) scaled as Mb-0.044. Hence, the total volume of mitochondria in heart, V(mt), scaled as Mb0 .927 (V(mt) = VV(mt,f) x Vh). The volume of heart mitochondria was found to scale disproportionately to VO2max ( Mb0 .75) but in proportion to resting cardiac work rate ( Mb0 .9).

Estimating length density and quantifying anisotropy in skeletal muscle capillaries.

The accurate estimation of stereological parameters defined on anisotropic structures is a long-standing problem. In this paper we seek to estimate the capillary length density JV in skeletal muscle tissue. A well-known model for directional anisotropy in space, namely the 'spherical normal' or 'Fisher axial distribution' model, is found to fit the relevant data satisfactorily. Based on this model, a short-cut estimation method is proposed and illustrated with a numerical example. This method essentially consists in taking the ratio of mean capillary profile counts, as obtained from transversal and longitudinal sections of the muscle tissue, and making use of a table or a graph given in the paper to estimate JV. The conditions under which the methods are applicable and practicable are discussed in detail. Apart from an accurate estimation of JV, an important feature of our method is the possibility of quantifying the degree of anisotropy by a coefficient K (called the concentration parameter of the Fisher axial distribution), which enjoys both a biological significance and a sound statistical basis.