We present a performance assessment of the European Integrated Carbon Observing System (ICOS) atmospheric network for constraining European biogenic CO.sub.2 fluxes (hereafter net ecosystem exchange, ...NEE). The performance of the network is assessed in terms of uncertainty in the fluxes, using a state-of-the-art mesoscale variational atmospheric inversion system assimilating hourly averages of atmospheric data to solve for NEE at 6 h and 0.5° resolution. The performance of the ICOS atmospheric network is also assessed in terms of uncertainty reduction compared to typical uncertainties in the flux estimates from ecosystem models, which are used as prior information by the inversion. The uncertainty in inverted fluxes is computed for two typical periods representative of northern summer and winter conditions in July and in December 2007, respectively. These computations are based on a observing system simulation experiment (OSSE) framework. We analyzed the uncertainty in a 2-week-mean NEE as a function of the spatial scale with a focus on the model native grid scale (0.5°), the country scale and the European scale (including western Russia and Turkey). Several network configurations, going from 23 to 66 sites, and different configurations of the prior uncertainties and atmospheric model transport errors are tested in order to assess and compare the improvements that can be expected in the future from the extension of the network, from improved prior information or transport models. Assimilating data from 23 sites (a network comparable to present-day capability) with errors estimated from the present prior information and transport models, the uncertainty reduction on a 2-week-mean NEE should range between 20 and 50 % for 0.5° resolution grid cells in the best sampled area encompassing eastern France and western Germany. At the European scale, the prior uncertainty in a 2-week-mean NEE is reduced by 50 % (66 %), down to ~ 43 Tg C month.sup.-1 (26 Tg C month.sup.-1) in July (December). Using a larger network of 66 stations, the prior uncertainty of NEE is reduced by the inversion by 64 % (down to ~ 33 Tg C month.sup.-1) in July and by 79 % (down to ~ 15 Tg C month.sup.-1) in December. When the results are integrated over the well-observed western European domain, the uncertainty reduction shows no seasonal variability. The effect of decreasing the correlation length of the prior uncertainty, or of reducing the transport model errors compared to their present configuration (when conducting real-data inversion cases) can be larger than that of the extension of the measurement network in areas where the 23 station observation network is the densest. We show that with a configuration of the ICOS atmospheric network containing 66 sites that can be expected on the long-term, the uncertainties in a 2-week-mean NEE will be reduced by up to 50-80 % for countries like Finland, Germany, France and Spain, which could significantly improvement (and at least a high complementarity to) our knowledge of NEE derived from biomass and soil carbon inventories at multi-annual scales.
Prenatal alcohol exposure has been shown to produce hyperresponsiveness of the hypothalamic‐pituitary‐adrenal (HPA) axis to immune challenges. Because cytokines, which are released in response to ...immune challenges, are known to activate the HPA axis, this study determined whether altered release of cytokines contribute to the HPA hyperresponsiveness to immune challenges observed after prenatal alcohol exposure. Pregnant dams were exposed to alcohol vapors (6‐7 hr daily) between days 7 and 18 of gestation. At postnatal days 45 and 60, control (C) and prenatal alcohol‐exposed (E) offspring were subjected to three different types of immune challenges: injections of interleukin‐1β or endotoxin (lipopolysaccharide), or turpentine‐induced tissue injury. We observed the expected higher plasma adrenocorticotropic hormone and corticosterone levels in E compared with C rats, and this HPA hyperresponsiveness was greater in E females compared with E males. Plasma tumor necrosis factor‐α or interleukin‐6 responses were comparable in the C and E groups. Females exhibited significantly higher corticosterone, tumor necrosis factor‐α, and interleukin‐6 responses than males. These results indicate that (1) prenatal alcohol exposure produces HPA hyperresponsiveness to immune challenges; (2) prenatal alcohol treatment does not influence the release of cytokines to immune challenges; and (3) there are gender differences in the secretory pattern of corticosterone and cytokines to immune challenges. Therefore, these data do not support the hypothesis that cytokines play a role in the hyperresponsiveness of the HPA axis to immune challenges observed after prenatal alcohol exposure.
This study sought to identify, by means of several analytical methods (GC-MS, HPLC-DAD, CE-DAD, FTIR, and NMR), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), which was found in two sets of tablets ...obtained from the Swiss black market. Unequivocal identification of 2C-B was only achieved by a combination of mass spectrometric and NMR analysis. Quantitation of 2C-B was performed by HPLC-DAD and CE-DAD. The amounts of 2C-B found in the tablets (3–8 mg) were in the range of the minimum quantity required to induce the effects characteristic of this drug.
The misuse of human growth hormone (hGH) in sport is deemed to be unethical and dangerous because of various adverse effects. Thus, it has been added to the International Olympic Committee list of ...banned substances. Until now, the very low concentration of hGH in the urine made its measurement difficult using classical methodology. Indeed, for routine diagnosis, only plasma measurements were available. However, unlike blood samples, urine is generally provided in abundant quantities and is, at present, the only body fluid allowed to be analysed in sport doping controls. A recently developed enzyme-linked immunosorbent assay (Norditest) makes it now possible, without any extraction, to measure urinary hGH (u-hGH) in a dynamic range of 2–50 ng hGH/1. In our protocol, untreated and treated non-athlete volunteers were followed. Some of them received therapeutical doses of recombinant hGH (Norditropin) for one week either intramuscularly (three increasing doses) or subcutaneously (12 I.U. every day). The u-hGH excretion after treatment showed dramatic increases of 50–100 times the basal values and returned to almost the mean normal level after 24 h. u-hGH was also measured in samples provided by the anti-doping controls at major and minor competitions. Depending on the type of efforts made during the competition, the hGH concentration in urine was dramatically increased. Insulin-like growth factor binding proteins and β2-microglobulins in urine and/or in blood could be necessary for the correct investigation of any hGH doping test procedure.
We determined whether the gas carbon monoxide (CO) altered the adrenocorticotropin hormone (ACTH) response to mild inescapable electrofootshocks, and whether it interacted with nitric oxide (NO). ...Peripheral injection of the NO synthase (NOS) inhibitor Nwnitro‐l‐arginine‐methylester (l‐NAME), a compound which readily crosses the blood–brain barrier, produced the expected blunting of the ACTH response to the shocks. This effect was mimicked by other arginine analogues such as l‐nitroarginine (l‐NNA) and NG‐methyl‐l‐arginine (NMMA). The subcutaneous (s.c.) administration of the heme oxygenase (HO) blockers tin mesoporphyrin (SnMP) or tin protoporphyrin (SnPP) significantly decreased brain HO levels, indicating that both compounds had penetrated the brain. Blood pressure showed a modest increase in response to SnMP, and no change after SnPP. SnMP and SnPP both decreased shock‐induced ACTH release, though the magnitude of this effect was slightly less than that of l‐NAME. The influence of SnPP was further augmented in rats with concomitant blockade of NO formation, which suggests that both NO and CO are necessary for the full response of this axis to electrofootshocks. Finally, the ability of SnPP to significantly blunt the expression of the mRNA for the immediate early gene NGFI‐B in the paraventricular nucleus (PVN) of rats exposed to shocks, indicates that the influence of CO was exerted on hypothalamic neuronal activity. Collectively, our results show that NO and CO exert a stimulatory effect on the HPA axis response to mild electrofootshocks, and that at least part of this influence takes place on hypothalamic neurons and/or their afferents.
A total of 53 urine samples were tested by different immunoassay methods and by gas chromatography/mass spectrometry to determine repeatability of the different methods and to assess whether the ...immunoassays performed on samples obtained from elderly patients of the emergency section could be considered as reliable enough for identifying a benzodiazepine consumption. Repeatability was excellent for GC/MS and good for immunoassays. The specificity was not different for the three immunoassays (96%). The sensitivity varied from 36, 64 to 75% for OnLine, RIA Immunalysis and RIA DPC, respectively. An other difference between immunoassays and GC/MS was the ability of GC/MS to detect lorazepam and low concentrations of benzodiazepines whereas immunoassays did not.
We sought to identify the brain circuitry that underlies the stimulatory role of nitric oxide (NO) role on the hypothalamic–pituitary–adrenal (HPA) axis. Specifically, we determined whether ...electrofootshocks (60 min) or the intravenous administration of lipopolysaccharide (LPS, 100 μg/kg)-activated neurocircuitries that express either neuronal NO synthase (nNOS), a constitutive enzyme responsible for NO formation, or
l-citrulline, an amino acid that is produced in equimolar amounts with NO. Shocks significantly increased the number of cells showing Fos immunoreactivity (ir) in the paraventricular nucleus (PVN) of the hypothalamus, the lateral hypothalamus (LH), amygdaloid complex (AD) and thalamus (TH), and to a lesser extent, in the hippocampus (HP), caudate putamen (CP) and frontal cortex (FC). However, shocks did not alter the number of nNOS-positive cells nor increased citrulline signals in these brain regions. LPS significantly upregulated the number of cells with fos-like ir in the PVN, LH, AD, TH, HP, CP and FC, but only increased the number of cells positive for citrulline in the PVN, 87% of which co-expressed Fos. Thus, while shocks did not alter nNOS gene expression or citrulline levels in the brain regions studied, LPS significantly increased the number of PVN cells expressing citrulline without concomitant changes in other brain areas. Endotoxemia also upregulated significantly more PVN cells that co-expressed Fos and nNOS, compared to shocks. As NO stimulates the PVN circuitries that participate in shocks- and LPS-induced ACTH release, the lack of changes in nNOS or citrulline levels due to shocks suggests that, in this model, constitutively formed NO may modulate HPA axis activity in the absence of changes in its synthesis.
In order to minimize the adverse effect of histamine release in the rat of some gonadotropin releasing hormone (GnRH) antagonists, such as Ac-D2Nal1,D4FPhe2,DTrp3,DArg6-GnRH, new structures with ...modifications at positions 1, 2, 3, 5, 6, 7, and 10 were synthesized and tested in several biological systems. In vitro: the affinity for the pituitary GnRH receptor was measured as was the ability of the analogues to inhibit GnRH-stimulated release of luteinizing hormone (LH) by dispersed anterior pituitary cells in culture and to release histamine from rat mast cells. In vivo: inhibition of ovulation in the cycling rat was determined after subcutaneous (sc) injection of the peptides at noon on the day of proestrus; the duration of action of the peptides was evaluated by measuring LH levels in the castrated male rat after sc injection of some selected analogues. Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,D-4-p-methoxy benzoyl-2-aminobutyric acid6,DAla10-GnRH was found to be one of the most potent analogues of this series, causing a 100% inhibition of ovulation at 5 micrograms/kg or less. Release of histamine was observed at doses 10-25 times that required for Ac-D2Nal1,D4FPhe2,DTrp3,DArg6-GnRH. Thus, introduction of arginine in position 5 with a hydrophobic amino acid in position 6 is compatible with high potency in several biological systems and results in compounds with lowered potency to release histamine compared to homologous peptides with tyrosine in position 5 and D-arginine in position 6.
Forensic scientists have long detected the presence of drugs and their metabolites in biological materials using body fluids such as urine, blood and/or other biological liquids or tissues. For ...doping analysis, only urine has so far been collected. In recent years, remarkable advances in sensitive analytical techniques have encouraged the analysis of drugs in unconventional biological samples such as hair, saliva and sweat. These samples are easily collected, although drug levels are often lower than the corresponding levels in urine or blood. This chapter reviews recent studies in the detection of doping agents in hair, saliva and sweat. Sampling, analytical procedures and interpretation of the results are discussed in comparison with those obtained from urine and blood samples.
A liquid chromatograpic method with UV detection was developed for the separation and quantification of six amphetamines in the presence of adulterants in illicit drugs. Comparison was made between a ...regular reversed-phase and a base-deactivated column. The mobile phase composition was optimized by studying the influence of pH, buffer composition and the organic solvent type. Validation was accomplished by examination of the linearity, precision, accuracy, limits of detection and limits of quantification of the method. Amphetamines were quantified in eight tablets obtained from illicit drug seizures and the results were verified by a GC-MS procedure.
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