115 research outputs found

    Cropping system effects on soil quality in the Great Plains: Synthesis from a regional project

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    Soils perform a number of essential functions affecting management goals. Soil functions were assessed by measuring physical, chemical, and biological properties in a regional assessment of conventional (CON) and alternative (ALT) management practices at eight sites within the Great Plains. The results, reported in accompanying papers, provide excellent data for assessing how management practices collectively affect agronomic and environmental soil functions that benefit both farmers and society. Our objective was to use the regional data as an input for two new assessment tools to evaluate their potential and sensitivity for detecting differences (aggradation or degradation) in management systems. The soil management assessment framework (SMAF) and the agro-ecosystem performance assessment tool (AEPAT) were used to score individual soil properties at each location relative to expected conditions based on inherent soil-forming factors and to compute index values that provide an overall assessment of the agronomic and environmental impact of the CON and ALT practices. SMAF index values were positively correlated with grain yield (an agronomic function) and total organic matter (an agronomic and environmental function). They were negatively correlated with soil nitrate concentration at harvest (an indicator of environmental function). There was general agreement between the two assessment tools when used to compare management practices. Users can measure a small number of soil properties and use one of these tools to easily assess the effectiveness of soil management practices. A higher score in either tool identifies more environmentally and agronomically sustainable management. Temporal variability in measured indicators makes dynamic assessments of management practices essential. Water-filled pore space, aggregate stability, particulate organic matter, and microbial biomass were sensitive to management and should be included in studies aimed at improving soil management. Reductions in both tillage and fallow combined with crop rotation has resulted in improved soil function (e.g., nutrient cycling, organic C content, and productivity) throughout the Great Plains

    First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

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    BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

    Do distribution volumes and clearances relate to tissue volumes and blood flows? A computer simulation

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    BACKGROUND: Kinetics of inhaled agents are often described by physiological models. However, many pharmacokinetic concepts, such as context-sensitive half-times, have been developed for drugs described by classical compartmental models. We derived classical compartmental models that describe the course of the alveolar concentrations (F(A)) generated by the physiological uptake and distribution models used by the Gas Man(® )program, and describe how distribution volumes and clearances relate to tissue volumes and blood flows. METHODS: Gas Man(® )was used to generate F(A )vs. time curves during the wash-in and wash-out period of 115 min each with a high fresh gas flow (8 L.min(-1)), a constant alveolar minute ventilation (4 L.min(-1)), and a constant inspired concentration (F(I)) of halothane (0.75%), isoflurane (1.15%), sevoflurane (2%), or desflurane (6%). With each of these F(I), simulations were ran for a 70 kg patient with 5 different cardiac outputs (CO) (2, 3, 5, 8 and 10 L.min(-1)) and for 5 patients with different weights (40, 55, 70, 85, and 100 kg) but the same CO (5 L.min(-1)). Two and three compartmental models were fitted to F(A )of the individual 9 runs using NONMEM. After testing for parsimony, goodness of fit was evaluated using median prediction error (MDPE) and median absolute prediction error (MDAPE). The model was tested prospectively for a virtual 62 kg patient with a cardiac output of 4.5 L.min(-1 )for three different durations (wash-in and wash-out period of 10, 60, and 180 min each) with an F(I )of 1.5% halothane, 1.5% isoflurane, sevoflurane 4%, or desflurane 12%. RESULTS: A three-compartment model fitted the data best (MDPE = 0% and MDAPE ≤ 0.074%) and performed equally well when tested prospectively (MDPE ≤ 0.51% and MDAPE ≤ 1.51%). The relationship between CO and body weight and the distribution volumes and clearances is complex. CONCLUSION: The kinetics of anesthetic gases can be adequately described e by a mammilary compartmental model. Therefore, concepts that are traditionally thought of as being applicable to the kinetics of intravenous agents can be equally well applied to anesthetic gases. Distribution volumes and clearances cannot be equated to tissue volumes and blood flows respectively

    Investigation of in vitro transdermal absorption of fentanyl from patches placed on skin samples obtained from various anatomic regions of dogs

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    Objective-To investigate in vitro transdermal absorption of fentanyl from patches through skin samples obtained from various anatomic regions of dogs. Sample Population-Skin samples from 5 Greyhounds. Procedure-Skin samples from the dogs' thoracic, neck, and groin regions were collected postmortem and frozen. After samples were thawed, circular sections were cut and placed in Franz-type diffusion cells in a water bath (32degreesC). A commercial fentanyl patch, attached to an acetate strip with a circular hole, was applied to each skin sample. Cellulose strips were used as control membranes. Samples of receptor fluid in the diffusion cells were collected at intervals for 48 hours, and fentanyl concentrations were analyzed by use of high-performance liquid chromatography. Results-Mean +/- SD release rate of fentanyl from the patch, defined by its absorption rate through the non-rate-limiting cellulose membrane, was linear during the first 8 hours (2.01 +/- 0.05 pg/cm(2) of cellulose membrane/h) and then decreased. Fentanyl passed through skin from the groin region at a faster rate and with a significantly shorter lag time, compared with findings in neck or thoracic skin samples. Conclusions and Clinical Relevance-In vitro, fentanyl from a patch was absorbed more quickly and to a greater extent through skin collected from the groin region of dogs, compared with skin samples from the thoracic and neck regions. Placement of fentanyl patches in the groin region of dogs may decrease the lag time to achieve analgesia perioperatively; however, in vivo studies are necessary to confirm these findings

    Evaluation of SLOG/TCI-III pediatric system on target control infusion of propofol

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    <p>Abstract</p> <p>Background</p> <p>The target-controlled infusion-III (SLOG/TCI-III) system was derived from a model set up by the local pediatric population for target control infusion of propofol.</p> <p>Methods</p> <p>The current study aimed at evaluating the difference between target concentrations of propofol and performance, which was measured using the SLOG/TCI-III system in children. Thirty children fulfilling the I-II criteria according to American Society of Anesthesiology were enrolled in the study. The target plasma concentration of propofol was fed into the SLOG/TCI-III system and compared with the measured concentrations of propofol. Blood samples were collected and analyzed by high performance liquid chromatography with fluorescence detector. The performance error (PE) was determined for each measured blood propofol concentration. The performances of the TCI-III system were determined by the median performance error (MDPE), the median absolute performance error (MDAPE), and Wobble (the median absolute deviation of each PE from the MDPE), respectively.</p> <p>Results</p> <p>Concentration against target concentration showed good linear correlation: concentration = 1.3428 target concentration - 0.2633 (r = 0.8667). The MDPE and MDAPE of the pediatric system were 10 and 22%, respectively, and the median value for Wobble was 24%. MDPE and MDAPE were less than 15 and 30%, respectively.</p> <p>Conclusions</p> <p>The performance of TCI-III system seems to be in the accepted limits for clinical practice in children.</p

    Multilocation Corn Stover Harvest Effects on Crop Yields and Nutrient Removal

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    Corn (Zea mays L.) stover was identified as an important feedstock for cellulosic bioenergy production because of the extensive area upon which the crop is already grown. This report summarizes 239 site-years of field research examining effects of zero, moderate, and high stover removal rates at 36 sites in seven different states. Grain and stover yields from all sites as well as N, P, and K removal from 28 sites are summarized for nine longitude and six latitude bands, two tillage practices (conventional vs no tillage), two stover-harvest methods (machine vs calculated), and two crop rotations {continuous corn (maize) vs corn/soybean [Glycine max (L.) Merr.]}. Mean grain yields ranged from 5.0 to 12.0 Mg ha−1 (80 to 192 bu ac−1). Harvesting an average of 3.9 or 7.2 Mg ha−1(1.7 or 3.2 tons ac−1) of the corn stover resulted in a slight increase in grain yield at 57 and 51 % of the sites, respectively. Average no-till grain yields were significantly lower than with conventional tillage when stover was not harvested, but not when it was collected. Plant samples collected between physiological maturity and combine harvest showed that compared to not harvesting stover, N, P, and K removal was increased by 24, 2.7, and 31 kg ha−1, respectively, with moderate (3.9 Mg ha−1) harvest and by 47, 5.5, and 62 kg ha−1, respectively, with high (7.2 Mg ha−1) removal. This data will be useful for verifying simulation models and available corn stover feedstock projections, but is too variable for planning site-specific stover harvest

    Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice

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    The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ9-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice. Abcb1a/b (−/−), Abcg2 (−/−) and wild-type (WT) mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (−/−) and Abcg2 (−/−) mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (−/−) mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis
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