The effects of prolonged exposure to elevated temperatures and elevated CO2 levels on the growth, yield and dry matter partitioning of field-sown meadow fescue

Selostus: Kohotetun lämpötilan ja kohotetun CO2-pitoisuuden vaikutukset peltoon kylvetyn nurminadan kasvuun, satoon ja kuiva-aineen jakautumiseen

Tobramycin exposure from active calcium sulfate bone graft substitute.

BACKGROUND: Bone graft substitute such as calcium sulfate are frequently used as carrier material for local antimicrobial therapy in orthopedic surgery. This study aimed to assess the systemic absorption and disposition of tobramycin in patients treated with a tobramycin-laden bone graft substitute (Osteoset® T). METHODS: Nine blood samples were taken from 12 patients over 10 days after Osteoset® T surgical implantation. Tobramycin concentration was measured by fluorescence polarization. Population pharmacokinetic analysis was performed using NONMEM to assess the average value and variability (CV) of pharmacokinetic parameters. Bioavailability (F) was assessed by equating clearance (CL) with creatinine clearance (Cockcroft CLCr). Based on the final model, simulations with various doses and renal function levels were performed. (ClinicalTrials.gov number, NCT01938417). RESULTS: The patients were 52 +/- 20 years old, their mean body weight was 73 +/- 17 kg and their mean CLCr was 119 +/- 55 mL/min. Either 10 g or 20 g Osteoset® T with 4% tobramycin sulfate was implanted in various sites. Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing important variability. With CL equated to CLCr, mean absorption rate constant (ka) was 0.06 h-1, F was 63% or 32% (CV 74%) for 10 and 20 g Osteoset® T respectively, and volume of distribution (V) was 16.6 L (CV 89%). Simulations predicted sustained high, potentially toxic concentrations with 10 g, 30 g and 50 g Osteoset® T for CLCr values below 10, 20 and 30 mL/min, respectively. CONCLUSIONS: Osteoset® T does not raise toxicity concerns in subjects without significant renal failure. The risk/benefit ratio might turn unfavorable in case of severe renal failure, even after standard dose implantation.

Sex differences in urinary levels of several biological indicators of exposure: a simulation study using a compartmental based toxicokinetic model

Toxicokinetic modeling is a useful tool to describe or predict the behavior of a chemical agent in the human or animal organism. A general model based on four compartments was developed in a previous study in order to quantify the effect of human variability on a wide range of biological exposure indicators. The aim of this study was to adapt this existing general toxicokinetic model to three organic solvents, which were methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1,-trichloroethane, and to take into account sex differences. We assessed in a previous human volunteer study the impact of sex on different biomarkers of exposure corresponding to the three organic solvents mentioned above. Results from that study suggested that not only physiological differences between men and women but also differences due to sex hormones levels could influence the toxicokinetics of the solvents. In fact the use of hormonal contraceptive had an effect on the urinary levels of several biomarkers, suggesting that exogenous sex hormones could influence CYP2E1 enzyme activity. These experimental data were used to calibrate the toxicokinetic models developed in this study. Our results showed that it was possible to use an existing general toxicokinetic model for other compounds. In fact, most of the simulation results showed good agreement with the experimental data obtained for the studied solvents, with a percentage of model predictions that lies within the 95% confidence interval varying from 44.4 to 90%. Results pointed out that for same exposure conditions, men and women can show important differences in urinary levels of biological indicators of exposure. Moreover, when running the models by simulating industrial working conditions, these differences could even be more pronounced. In conclusion, a general and simple toxicokinetic model, adapted for three well known organic solvents, allowed us to show that metabolic parameters can have an important impact on the urinary levels of the corresponding biomarkers. These observations give evidence of an interindividual variablity, an aspect that should have its place in the approaches for setting limits of occupational exposure.

Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists.

Measurements and simulations were performed to assess workers' exposure to solvent vapors and aerosols during the waterproofing of a tiled surface. This investigation followed two recent incidents in the same company where workers experienced acute respiratory illness after spraying a stain-repellent resin containing fluorinated polymers on stone-tiled walls and floors. Because the waterproofing activity had been done for years at the tile company without encountering any exposure problems prior to these cases, it was strongly suspected that the incidents were linked to a recent change in the composition of the coating mixture. Experimental measurements and simulations indicated that the emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The measurement of the solvent emission rate from surfaces coated with the two resins indicated that shortly after spraying, the emission was in the range of 18 to 20 mg/sec x m2 and was similar for both products. Solvent and overspray emission rates were introduced in a two-zone compartment model. The results obtained in the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3 for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also shown that the introduction of the new resin tended to significantly decrease the levels of solvents and particulates in the workers' breathing zone. These results strongly suggest that cases of acute respiratory illness are related to the specific toxicity of the fluorinated polymer itself. The fact that the same polymer is used in various commercial products raises concern regarding other possible occupational and domestic exposures.

Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.

Reversible and irreversible pollutant-induced bacterial cellular stress effects measured by ethidium bromide uptake and efflux.

Chemical pollution is known to affect microbial community composition but it is poorly understood how toxic compounds influence physiology of single cells that may lay at the basis of loss of reproductive fitness. Here we analyze physiological disturbances of a variety of chemical pollutants at single cell level using the bacterium Pseudomonas fluorescens in an oligotrophic growth assay. As a proxy for physiological disturbance we measured changes in geometric mean ethidium bromide (EB) fluorescence intensities in subpopulations of live and dividing cells exposed or not exposed to different dosages of tetradecane, 4-chlorophenol, 2-chlorobiphenyl, naphthalene, benzene, mercury chloride, or water-dissolved oil fractions. Because ethidium bromide efflux is an energy-dependent process any disturbance in cellular energy generation is visible as an increased cytoplasmic fluorescence. Interestingly, all pollutants even at the lowest dosage of 1 nmol/mL culture produced significantly increased ethidium bromide fluorescence compared to nonexposed controls. Ethidium bromide fluorescence intensities increased upon pollutant exposure dosage up to a saturation level, and were weakly (r(2) = 0.3905) inversely correlated to the proportion of live cells at that time point in culture. Temporal increase in EB fluorescence of growing cells is indicative for toxic but reversible effects. Cells displaying high continued EB fluorescence levels experience constant and permanent damage, and no longer contribute to population growth. The procedure developed here using bacterial ethidium bromide efflux pump activity may be a useful complement to screen sublethal toxicity effects of chemicals.

Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study.

Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first-trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8-2.7]), minor birth defects (1.3 [0.4-3.7]), and major birth defects (1.8 [0.6-5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3-fold (3.4 [1.5-7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.

Assessment of bioaerosols and inhalable dust exposure in Swiss sawmills

An assessment of wood workers' exposure to airborne cultivable bacteria, fungi, inhalable endotoxins and inhalable organic dust was performed at 12 sawmills that process mainly coniferous wood species. In each plant, samples were collected at four or five different work sites (debarking, sawing, sorting, planing and sawing cockpit) and the efficiency of sampling devices (impinger or filter) for determining endotoxins levels was evaluated. Results show that fungi are present in very high concentrations (up to 35 000 CFU m(-3)) in all sawmills. We also find that there are more bioaerosols at the sorting work site (mean +/- SD: 7723 +/- 9919 CFU m(-3) for total bacteria, 614 +/- 902 CFU m(-3) for Gram-negative, 19 438 +/- 14 246 CFU m(-3) for fungi, 7.0 +/- 9.0 EU m(-3) for endotoxin and 2.9 +/- 4.8 g m(-3) for dust) than at the sawing station (mean +/- SD: 1938 +/- 2478 CFU m(-3) for total bacteria, 141 +/- 206 CFU m(-3) for Gram-negative, 12 207 +/- 10 008 CFU m(-3) for fungi, 2.1 +/- 1.9 EU m(-3) for endotoxin and 0.75 +/- 0.49 mg m(-3) for dust). At the same time, the species composition and concentration of airborne Gram-negative bacteria were studied. Penicillinium sp. were the predominant fungi, while Bacillus sp. and the Pseudomonadacea family were the predominant Gram-positive and Gram-negative bacteria encountered, respectively. [Authors]

Microstructure of highly oriented, hexagonal, boron nitride thin films grown on crystalline silicon by radio frequency plasma-assisted chemical vapor deposition

We present a high‐resolution electron microscopy study of the microstructure of boron nitride thin films grown on silicon (100) by radio‐frequency plasma‐assisted chemical vapor deposition using B2H6 (1% in H2) and NH3 gases. Well‐adhered boron nitride films grown on the grounded electrode show a highly oriented hexagonal structure with the c‐axis parallel to the substrate surface throughout the film, without any interfacial amorphous layer. We ascribed this textured growth to an etching effect of atomic hydrogen present in the gas discharge. In contrast, films grown on the powered electrode, with compressive stress induced by ion bombardment, show a multilayered structure as observed by other authors, composed of an amorphous layer, a hexagonal layer with the c‐axis parallel to the substrate surface and another layer oriented at random

Gas collisions and pressure quenching of the photoluminescence of silicon nanopowder grown by plasma-enhanced chemical vapor deposition

The quenching of the photoluminescence of Si nanopowder grown by plasma-enhanced chemical vapor deposition due to pressure was measured for various gases ( H2, O2, N2, He, Ne, Ar, and Kr) and at different temperatures. The characteristic pressure, P0, of the general dependence I(P) = I0¿exp(¿P/P0) is gas and temperature dependent. However, when the number of gas collisions is taken as the variable instead of pressure, then the quenching is the same within a gas family (mono- or diatomic) and it is temperature independent. So it is concluded that the effect depends on the number of gas collisions irrespective of the nature of the gas or its temperature.

Computer-aided procedure for optimization of layer thickness uniformity in thermal evaporation physical vapor deposition chambers for lens coating

A computer-aided method to improve the thickness uniformity attainable when coating multiple substrates inside a thermal evaporation physical vapor deposition unit is presented. The study is developed for the classical spherical (dome-shaped) calotte and also for a plane sector reversible holder setup. This second arrangement is very useful for coating both sides of the substrate, such as antireflection multilayers on lenses. The design of static correcting shutters for both kinds of configurations is also discussed. Some results of using the method are presented as an illustration.

Exposition aux immunosuppresseurs in utero [Exposure in utero to immunosuppressives]

The number of pregnant women receiving immunosuppressive therapy is increasing. Use of immunosuppressants during pregnancy is indicated for anti-rejection therapy in transplantation patients and treatment of autoimmune diseases. Despite the maternal and fetal risks of these pregnancies, the proportion of surviving infants is improving and the possibility that a pregnancy could occur in these women during their childbearing years should be considered. All immunosuppressant drugs and their metabolites cross the placenta, raising questions about the long-term outcome of the children exposed to these agents in utera. There is no increased risk of congenital anomalies. However, there is an elevated incidence of prematurity, intrauterine growth retardation (IUGR) and therefore low birthweight, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporin, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes. The follow-up of these infants should be carefully organized and multidisciplinary, taking the perinatal context into account.