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Mean Residence Time (mean + residence_time)
Selected AbstractsSequestration and turnover of plant- and microbially derived sugars in a temperate grassland soil during 7 years exposed to elevated atmospheric pCO2GLOBAL CHANGE BIOLOGY, Issue 2 2007MICHAEL BOCK Abstract Temperate grasslands contribute about 20% to the global terrestrial carbon (C) budget with sugars contributing 10,50% to this soil C pool. Whether the observed increase of the atmospheric CO2 concentration (pCO2) leads to additional C sequestration into these ecosystems or enhanced mineralization of soil organic matter (SOM) is still unclear. Therefore, the aim of the presented study was to investigate the impact of elevated atmospheric pCO2 on C sequestration and turnover of plant- (arabinose and xylose) and microbially derived (fucose, rhamnose, galactose, mannose) sugars in soil, representing a labile SOM pool. The study was carried out at the Swiss Free Air Carbon Dioxide Enrichment (FACE) experiment near Zurich. For 7 years, Lolium perenne swards were exposed to ambient and elevated pCO2 (36 and 60 Pa, respectively). The additional CO2 in the FACE plots was depleted in 13C compared with ambient plots, so that ,new' (<7 years) C inputs could be determined by means of compound-specific stable isotope analysis (13C : 12C). Samples were fractionated into clay, silt, fine sand and coarse sand, which yielded relatively stable and labile SOM pools with different turnover rates. Total sugar sequestration into bulk soil after 7 years of exposure to elevated pCO2 was about 28% compared with the control plots. In both ambient and elevated plots, total sugar concentrations in particle size fractions increased in the order sand Pharmacokinetic and pharmacodynamic properties of metomidate in turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus)JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003M. K. Hansen Metomidate was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously at a dose of 3 mg/kg bodyweight, as a bath treatment at a dose of 9 mg/L water for 5 min to study the disposition of metomidate, and as bath treatment (9 mg/L) for 10 min to study the absorption and effect of metomidate on respiration and balance/motor control. Additionally, turbot were given metomidate orally at a dose of 7 mg/kg. The studies were performed in seawater at a temperature of 10.3 ± 0.4 °C (halibut) and 18.0 ± 0.3 °C (turbot). Pharmacokinetic modeling of the data showed that metomidate had shorter elimination half-life and higher plasma concentrations in turbot compared with halibut, both species displaying a rapid uptake, distribution and excretion. Following intravenous administration, the volumes of distribution at steady state (Vd(ss)) were 0.21 L/kg (halibut) and 0.44 L/kg (turbot). Plasma clearances (Cl) were 0.099 L/h·kg in halibut and 0.26 L/h·kg in turbot and the elimination half-lives (t½,z) were calculated to be 5.8 h and 2.2 h in halibut and turbot, respectively. Mean residence times (MRT) were 2.2 h in halibut and 1.7 h in turbot. Following oral administration, the t½,z was 3.5 h in turbot. The maximum plasma concentration (Cmax) was 7.8 mg/L in turbot 1 h after administration. The oral bioavailability (F) was calculated to 100% in turbot. Following 5 min bath the maximum plasma concentrations (Cmax), which were observed immediately after end of the bath, were 9.5 mg/L and 13.3 mg/L in halibut and turbot, respectively. Metomidate rapidly immobilized the fish, with respiratory depression, reduced heart rate, and loss of balance/motor control within 1 min (mean). Recovery was slow, with resumed balance/motor control after 26.4 min. Opercular respiration movements were resumed more rapidly with a recorded mean of 1.7 min. Oral administration was demonstrated to be a way of immobilizing fish, for example in large aquariums, without exposing them to unwanted stress. [source] Behavior of fully filled regions in a non-intermeshing twin-screw extruderPOLYMER ENGINEERING & SCIENCE, Issue 8 2003Rajath Mudalamane Twin-screw extruders are operated with sequential filled and partially filled regions in order to perform the required unit processes. Channel fill length, defined as the length of fully filled regions in an extrusion screw, is gaining importance as a design parameter because of its implications on residence time distribution, distributive and dispersive mixing, and also process stability. A detailed study,experimental and theoretical,of the behavior of fill lengths in response to operating conditions (throughput, screw speed) and screw geometry is presented in this paper. Mean residence times were also measured for each geometry and operating condition. The apparatus consisted of a non-intermeshing counter-rotating twin-screw extruder (NITSE) with a transparent (acrylic) barrel, fed with corn syrup (Newtonian at room temperature). Fill length exhibits a nonlinear relationship with specific throughput (Q/N), with the slope increasing monotonously as the throughput Q increases at a given screw speed N. The mean residence time exhibits a strong linear relationship with inverse specific throughput and inverse fill length. A theoretical model was developed to predict the filled length based on pressure-throughput relationships taken from literature for this system, and the predictions were found to agree very well with experimental observations. [source] Pharmacokinetics of Levetiracetam and Its Enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide in DogsEPILEPSIA, Issue 7 2001Nina Isoherranen Summary: ,Purpose: The new antiepileptic drug, levetiracetam (LEV, ucb LO59), is a chiral molecule with one asymmetric carbon atom whose anticonvulsant activity is highly enantioselective. The purpose of this study was to evaluate and compare the pharmacokinetics (PK) of LEV [(S)-,-ethyl-2-oxo-pyrrolidine acetamide] and its enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide (REV) after i.v. administration to dogs. This is the first time that the pharmacokinetics of both enantiomers has been evaluated. Methods: Optically pure LEV and REV were synthesized, and 20 mg/kg of individual enantiomers was administered intravenously to six dogs. Plasma and urine samples were collected until 24 h, and the concentrations of LEV and REV were determined by an enantioselective assay. The levels of 2-pyrrolidone- N -butyric acid, an acid metabolite of LEV and REV, were determined by high-performance liquid chromatography (HPLC). The data were used for PK analysis of LEV and REV. Results: LEV and REV had similar mean ± SD values for clearance; 1.5 ± 0.3 ml/min/kg and volume of distribution; 0.5 ± 0.1 L/kg. The half-life (t1/2) and mean residence time (MRT) of REV (t1/2, 4.3 ± 0.8 h, and MRT, 6.0 ± 1.1 h) were, however, significantly longer than those of LEV (t1/2, 3.6 ± 0.8 h, and MRT, 5.0 ± 1.2 h). The renal clearance and fraction excreted unchanged for LEV and REV were significantly different. Conclusions: In addition to the enantioselective pharmacodynamics, ,-ethyl-2-oxo-pyrrolidine acetamide has enantioselective PK. The enantioselectivity was observed in renal clearance. Because REV has more favorable PK in dogs than LEV, the higher antiepileptic potency of LEV is more likely due to intrinsic pharmacodynamic activity rather than to enantioselective PK. [source] Pharmacokinetics of detomidine administered to horses at rest and after maximal exerciseEQUINE VETERINARY JOURNAL, Issue 5 2009J. A. E. HUBBELL Summary Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect. [source] Quantifying root lateral distribution and turnover using pine trees with a distinct stable carbon isotope signatureFUNCTIONAL ECOLOGY, Issue 1 2005K. JOHNSEN Summary 1In order to help assess spatial competition for below-ground resources, we quantified the effects of fertilization on root biomass quantity and lateral root distribution of mid-rotation Pinus taeda trees. Open-top chambers exposed trees to ambient or ambient plus 200 µmol mol,1 atmospheric CO2 for 31 months. 2Tank CO2 was depleted in atmospheric 13C; foliage of elevated CO2 trees had ,13C of ,42·9, compared with ,29·1 for ambient CO2 trees. 3Roots 1 m from the base of elevated CO2 -grown trees had more negative ,13C relative to control trees, and this difference was detected, on average, up to 5·8, 3·7 and 3·7 m away from the trees for 0,2, 2,5 and >5 mm root-size classes, respectively. Non-fertilized tree roots extended as far as fertilized trees despite the fact that their above-ground biomass was less than half that of fertilized trees. 4These results are informative with respect to root sampling intensity and protocol, and the distances required between experimental manipulations to evaluate below-ground processes of independent treatments. 5Fine-root turnover has usually been estimated to range from weeks to 3 years, representing a major avenue of carbon flux. Using a mixing model we calculated that 0,2 mm roots had a mean residence time of 4·5 years indicating relatively slow fine-root turnover, a result that has major implications in modelling C cycling. [source] Spring temperatures in the Sagehen Basin, Sierra Nevada, CA: implications for heat flow and groundwater circulationGEOFLUIDS (ELECTRONIC), Issue 3 2009MARIA BRUMM Abstract Heat flow in the Sierra Nevada, CA, is low despite its young geologic age. We investigate the possibility that advective heat transport by groundwater flow leads to an underestimate of heat flow in the Sierras based purely on borehole measurements. Using temperature and discharge measurements at springs in Sagehen Basin, we find that groundwater removes the equivalent of approximately 20,40 mW m,2 of geothermal heat from the basin. This is comparable with other heat flow measurements in the region and indicates that, in this basin, at least, groundwater does transport a significant amount of geothermal heat within the basin. Additionally, we use estimates of the mean residence time of water discharged at the springs along with hourly temperature records in springs to provide constraints on groundwater flow depths within the basin. An analytical model based on these constraints indicates that the heat removed by groundwater may represent 20% to >90% of the total heat flow in the basin. Without better constraints on the regional hydrogeology and the depth of circulation, we cannot determine whether the heat discharged at the springs represents a change in the mode of heat transfer, i.e. from conduction to advection at shallow depths (<100 m) or whether this is a component of heat transfer that should be added to measured conductive values. If the latter is true, and Sagehen Basin is representative of the Sierras, basal heat flow in the Sierra Nevada may be higher than previously thought. [source] Sources of plant-derived carbon and stability of organic matter in soil: implications for global changeGLOBAL CHANGE BIOLOGY, Issue 8 2009SUSAN E. CROW Abstract Alterations in forest productivity and changes in the relative proportion of above- and belowground biomass may have nonlinear effects on soil organic matter (SOM) storage. To study the influence of plant litter inputs on SOM accumulation, the Detritus Input Removal and Transfer (DIRT) Experiment continuously alters above- and belowground plant inputs to soil by a combination of trenching, screening, and litter addition. Here, we used biogeochemical indicators [i.e., cupric oxide extractable lignin-derived phenols and suberin/cutin-derived substituted fatty acids (SFA)] to identify the dominant sources of plant biopolymers in SOM and various measures [i.e., soil density fractionation, laboratory incubation, and radiocarbon-based mean residence time (MRT)] to assess the stability of SOM in two contrasting forests within the DIRT Experiment: an aggrading deciduous forest and an old-growth coniferous forest. In the deciduous forest, removal of both above- and belowground inputs increased the total amount of SFA over threefold compared with the control, and shifted the SFA signature towards a root-dominated source. Concurrently, light fraction MRT increased by 101 years and C mineralization during incubation decreased compared with the control. Together, these data suggest that root-derived aliphatic compounds are a source of SOM with greater relative stability than leaf inputs at this site. In the coniferous forest, roots were an important source of soil lignin-derived phenols but needle-derived, rather than root-derived, aliphatic compounds were preferentially preserved in soil. Fresh wood additions elevated the amount of soil C recovered as light fraction material but also elevated mineralization during incubation compared with other DIRT treatments, suggesting that not all of the added soil C is directly stabilized. Aboveground needle litter additions, which are more N-rich than wood debris, resulted in accelerated mineralization of previously stored soil carbon. In summary, our work demonstrates that the dominant plant sources of SOM differed substantially between forest types. Furthermore, inputs to and losses from soil C pools likely will not be altered uniformly by changes in litter input rates. [source] Assessing the effect of elevated carbon dioxide on soil carbon: a comparison of four meta-analysesGLOBAL CHANGE BIOLOGY, Issue 8 2009BRUCE A. HUNGATE Abstract Soil is the largest reservoir of organic carbon (C) in the terrestrial biosphere and soil C has a relatively long mean residence time. Rising atmospheric carbon dioxide (CO2) concentrations generally increase plant growth and C input to soil, suggesting that soil might help mitigate atmospheric CO2 rise and global warming. But to what extent mitigation will occur is unclear. The large size of the soil C pool not only makes it a potential buffer against rising atmospheric CO2, but also makes it difficult to measure changes amid the existing background. Meta-analysis is one tool that can overcome the limited power of single studies. Four recent meta-analyses addressed this issue but reached somewhat different conclusions about the effect of elevated CO2 on soil C accumulation, especially regarding the role of nitrogen (N) inputs. Here, we assess the extent of differences between these conclusions and propose a new analysis of the data. The four meta-analyses included different studies, derived different effect size estimates from common studies, used different weighting functions and metrics of effect size, and used different approaches to address nonindependence of effect sizes. Although all factors influenced the mean effect size estimates and subsequent inferences, the approach to independence had the largest influence. We recommend that meta-analysts critically assess and report choices about effect size metrics and weighting functions, and criteria for study selection and independence. Such decisions need to be justified carefully because they affect the basis for inference. Our new analysis, with a combined data set, confirms that the effect of elevated CO2 on net soil C accumulation increases with the addition of N fertilizers. Although the effect at low N inputs was not significant, statistical power to detect biogeochemically important effect sizes at low N is limited, even with meta-analysis, suggesting the continued need for long-term experiments. [source] Partitioning sources of soil respiration in boreal black spruce forest using radiocarbonGLOBAL CHANGE BIOLOGY, Issue 2 2006Edward A.G. Schuur Abstract Separating ecosystem and soil respiration into autotrophic and heterotrophic component sources is necessary for understanding how the net ecosystem exchange of carbon (C) will respond to current and future changes in climate and vegetation. Here, we use an isotope mass balance method based on radiocarbon to partition respiration sources in three mature black spruce forest stands in Alaska. Radiocarbon (,14C) signatures of respired C reflect the age of substrate C and can be used to differentiate source pools within ecosystems. Recently-fixed C that fuels plant or microbial metabolism has ,14C values close to that of current atmospheric CO2, while C respired from litter and soil organic matter decomposition will reflect the longer residence time of C in plant and soil C pools. Contrary to our expectations, the ,14C of C respired by recently excised black spruce roots averaged 14, greater than expected for recently fixed photosynthetic products, indicating that some portion of the C fueling root metabolism was derived from C storage pools with turnover times of at least several years. The ,14C values of C respired by heterotrophs in laboratory incubations of soil organic matter averaged 60, higher than the contemporary atmosphere ,14CO2, indicating that the major contributors to decomposition are derived from a combination of sources consistent with a mean residence time of up to a decade. Comparing autotrophic and heterotrophic ,14C end members with measurements of the ,14C of total soil respiration, we calculated that 47,63% of soil CO2 emissions were derived from heterotrophic respiration across all three sites. Our limited temporal sampling also observed no significant differences in the partitioning of soil respiration in the early season compared with the late season. Future work is needed to address the reasons for high ,14C values in root respiration and issues of whether this method fully captures the contribution of rhizosphere respiration. [source] Role of lakes for organic carbon cycling in the boreal zoneGLOBAL CHANGE BIOLOGY, Issue 1 2004Grete Algesten Abstract We calculated the carbon loss (mineralization plus sedimentation) and net CO2 escape to the atmosphere for 79 536 lakes and total running water in 21 major Scandinavian catchments (size range 437,48 263 km2). Between 30% and 80% of the total organic carbon that entered the freshwater ecosystems was lost in lakes. Mineralization in lakes and subsequent CO2 emission to the atmosphere was by far the most important carbon loss process. The withdrawal capacity of lakes on the catchment scale was closely correlated to the mean residence time of surface water in the catchment, and to some extent to the annual mean temperature represented by latitude. This result implies that variation of the hydrology can be a more important determinant of CO2 emission from lakes than temperature fluctuations. Mineralization of terrestrially derived organic carbon in lakes is an important regulator of organic carbon export to the sea and may affect the net exchange of CO2 between the atmosphere and the boreal landscape. [source] Enhancement of haemostatic efficacy of plasma-derived FVIII by formulation with PEGylated liposomesHAEMOPHILIA, Issue 5 2009I. DAYAN Summary., We have shown previously that PEGylated liposomes (PEGLip) bind recombinant FVIII (rFVIII) with high affinity and specificity. This binding resulted in a significant extension of the biological activity of rFVIII as demonstrated in animal models and in clinical trials. In the present study we found that PEGLip bind plasma-derived factor VIII (pdFVIII). PEGLip binding did not affect potency or stability in vitro and did not alter levels of FVIII activity in vivo immediately after injection. However, formulation of pdFVIII with PEGLip led to several important improvements. Twenty-four and 30 hours after injection, FVIII activity levels were significantly higher in haemophilic mice injected with PEGLip-pdFVIII than in mice injected with standard pdFVIII. Half life, area under the curve and mean residence time were increased while clearance was decreased. In vivo efficacy was evaluated in a tail vein transection assay performed in haemophilic mice. Prophylactic treatment with PEGLip-pdFVIII was much more effective in prolonging survival in this assay than similar treatment with standard pdFVIII. These results suggest that formulation of pdFVIII with PEGLip has the potential to improve patient care by prolonging the biological efficacy of pdFVIII and reducing the frequency of FVIII infusions. [source] Assessing the impact of mixing assumptions on the estimation of streamwater mean residence timeHYDROLOGICAL PROCESSES, Issue 12 2010Fabrizio Fenicia Abstract Catchment streamwater mean residence time (Tmr) is an important descriptor of hydrological systems, reflecting their storage and flow pathway properties. Tmr is typically inferred from the composition of stable water isotopes (oxygen-18 and deuterium) in observed rainfall and discharge. Currently, lumped parameter models based on convolution and sinewave functions are usually used for tracer simulation. These traditional models are based on simplistic assumptions that are often known to be unrealistic, in particular, steady flow conditions, linearity, complete mixing and others. However, the effect of these assumptions on Tmr estimation is seldom evaluated. In this article, we build a conceptual model that overcomes several assumptions made in traditional mixing models. Using data from the experimental Maimai catchment (New Zealand), we compare a complete-mixing (CM) model, where rainfall water is assumed to mix completely and instantaneously with the total catchment storage, with a partial-mixing (PM) model, where the tracer input is divided between an ,active' and a ,dead' storage compartment. We show that the inferred distribution of Tmr is strongly dependent on the treatment of mixing processes and flow pathways. The CM model returns estimates of Tmr that are well identifiable and are in general agreement with previous studies of the Maimai catchment. On the other hand, the PM model,motivated by a priori catchment insights,provides Tmr estimates that appear exceedingly large and highly uncertain. This suggests that water isotope composition measurements in rainfall and discharge alone may be insufficient for inferring Tmr. Given our model hypothesis, we also analysed the effect of different controls on Tmr. It was found that Tmr is controlled primarily by the storage properties of the catchment, rather than by the speed of streamflow response. This provides guidance on the type of information necessary to improve Tmr estimation. Copyright © 2010 John Wiley & Sons, Ltd. [source] Steady- and unsteady-state lumped parameter modelling of tritium and chlorofluorocarbons transport: hypothetical analyses and application to an alpine karst aquiferHYDROLOGICAL PROCESSES, Issue 17 2005N. Nur Ozyurt Abstract Determination of a groundwater's mean residence time with the aid of environmental tracers is common in hydrogeology. Many of the lumped parameter (LP) applications used for this purpose have been based on steady-state models. However, the results may be misleading if a steady LP model is used to simulate the environmental tracer transport in an unsteady aquifer. To test this hypothesis, the results of steady and unsteady versions of several LP models were evaluated theoretically and in an alpine karst aquifer case by using tritium, oxygen-18 and chlorofluorocarbons (CFCs). The results reveal that the mean residence times obtained may be significantly different between the steady and unsteady versions of the same model. For the karst aquifer investigated, a serially connected exponential and a plug flow model were run under unsteady conditions. It is shown that outflux calibration with an unsteady model provides a firm basis in evaluating the results of models. An outflux-calibrated unsteady model predicted reasonably the observed series of water isotopes. The calibrated model's CFCs output overpredicts the observed concentrations, probably because of the time lag in the unsaturated zone of the alpine karst aquifer. Copyright © 2005 John Wiley & Sons, Ltd. [source] The gas-phase oxidation of n -hexadecaneINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 10 2001R. Fournet Since n -hexadecane or cetane is a reference fuel for the estimation of cetane numbers in diesel engines, a detailed chemical model of its gas-phase oxidation and combustion will help to enhance diesel performance and reduce the emission of pollutants at their outlet. However, until recently the gas-phase reactions of n -hexadecane had not been experimentally studied, prohibiting a validation of oxidation models which could be written. This paper presents a modeling study of the oxidation of n -hexadecane based on experiments performed in a jet-stirred reactor, at temperatures ranging from 1000 to 1250 K, 1-atm pressure, a constant mean residence time of 0.07 s, and high degree of nitrogen dilution (0.03 mol% of fuel) for equivalence ratios equal to 0.5, 1, and 1.5. A detailed kinetic mechanism was automatically generated by using the computer package (EXGAS) developed in Nancy. The long linear chain of this alkane necessitates the use of a detailed secondary mechanism for the consumption of the alkenes formed as a result of primary parent fuel decomposition. This high-temperature mechanism includes 1787 reactions and 265 species, featuring satisfactory agreement for both the consumption of reactants and the formation of products. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 574,586, 2001 [source] Determination of twin-screw extruder operational conditions for the preparation of thermoplastic vulcanizates on the basis of batch-mixer resultsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008F. Goharpey Abstract In this study, we attempted to prepare a thermoplastic vulcanizate in a twin-screw extruder by determining the screw configuration on the basis of batch-mixer results. In this regard, two sets of information were used: (1) the time length, power consumption, and filling factor of different stages of the reactive blending process in the internal mixer and (2) the mean residence time and power consumption of the twin-screw extruder. Morphological features of the samples taken from the melt-mixing and dynamic vulcanization zones of the extruder with the selected screw configuration were found to be comparable with corresponding samples taken from an internal mixer reported in our previous study. The rheological and mechanical properties could provide valuable information to support the reliability of this study. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Effect of temperature on pharmacokinetics of enrofloxacin in mud crab, Scylla serrata (Forsskål), following oral administrationJOURNAL OF FISH DISEASES, Issue 3 2008W H Fang Abstract The study was conducted to evaluate the pharmacokinetics of enrofloxacin following a single oral gavage (10 mg kg,1) in mud crab, Scylla serrata, at water temperatures of 19 and 26 °C. Enrofloxacin concentration in haemolymph was determined using high-performance liquid chromatography (HPLC). A multiple and repeated haemolymph sampling from the articular cavity of crab periopods was developed. The haemolymph of an individual crab was successfully sampled up to 11 times from the articular cavity. The profile of haemolymph enrofloxacin concentration of an individual crab versus time was thus achieved. The mean haemolymph enrofloxacin concentration versus time was described by a two-compartment model with first-order absorption at two water temperatures. The peak concentrations of haemolymph enrofloxacin at 19 and 26 °C were 7.26 and 11.03 ,g mL,1, at 6 and 2 h, respectively. The absorption and distribution half-life time ( and t1/2,) at 19 °C were 3.7 and 4.5 h, respectively, which were markedly larger than the corresponding values (1.1 and 1.5 h) at 26 °C; the elimination half-life time (t1/2,) was 79.1 and 56.5 h at 19 and 26 °C, respectively. The area under curve (AUC), total body clearance (Cl) and mean residence time (MRT0,,) at 19 °C were 636.0 mg L,1 h, 0.016 L h,1 kg,1 and 102.5 h, respectively; the corresponding values at 26 °C were 583.4 mg L,1 h, 0.018 L h,1 kg,1and 63.7 h. These results indicate that enrofloxacin is absorbed and eliminated more rapidly in mud crab at 26 °C than at 19 °C. [source] PROPERTIES of CROSS-LINKED STARCH PRODUCED IN A SINGLE SCREW EXTRUDER WITH and WITHOUT A MIXING ELEMENTJOURNAL OF FOOD PROCESS ENGINEERING, Issue 1 2004M. SEKER ABSTRACT Starch was extruded with sodium hydroxide and sodium trimetaphosphate in order to cross-link it in a single-screw extruder with and without a mixing element at constant screw speed of 90 rpm in the first set of experiments and at similar mean residence time controlled by screw speed in the second set of experiments. For the screw without mixing element in the second set of experiments, screw speed was adjusted to give the similar residence time as the single-screw extruder with mixing element at 220 rpm. Phosphorus content and pasting curves of extrudates showed that starch was cross-linked during extrusion. Replacing the screw without mixing element by the screw with mixing [source] A Review on Residence Time Distribution (RTD) in Food Extruders and Study on the Potential of Neural Networks in RTD ModelingJOURNAL OF FOOD SCIENCE, Issue 6 2002G. Ganjyal ABSTRACT: Residence time distribution and mean residence time depend on process variables, namely feed rate, screw speed, feed moisture content, barrel temperature, die temperature and die diameter. Flow in an extruder has been modeled by simulating residence time distribution, assuming the extruder to be a series of continuous-stirred-tank or plug-flow reactors. Others have developed relationships for mean residence time as functions of process variables. Better models can be developed using neural networks. As an example, data from the literature were used to model mean residence time as a function of process variables using statistical regression and neural networks. Neural network models performed better than regression models. [source] Continuous process for production of hydrogenated nitrile butadiene rubber using a Kenics® KMX static mixer reactorAICHE JOURNAL, Issue 11 2009Chandra Mouli R. Madhuranthakam Abstract A continuous process for hydrogenating nitrile butadiene rubber (NBR) was developed and its performance was experimentally investigated. A Kenics® KMX static mixer (SM) is used in the process as a gas,liquid reactor in which gaseous hydrogen reacts with NBR in an organic solution catalyzed by an organometallic complex such as an osmium complex catalyst. The Kenics® KMX SM was designed with 24 mixing elements with 3.81 cm diameter and arranged such that the angle between two neighboring elements is 90°. The internal structure of each element is open blade with the blades being convexly curved. The dimensions of the SM reactor are: 3.81 cm ID 80 S and 123 cm length and was operated cocurrently with vertical upflow. The NBR solutions of different concentrations (0.418 and 0.837 mol/L with respect to [CC]) were hydrogenated by using different concentrations of the osmium catalyst solution at various residence times. The reactions were conducted at a constant temperature of 138°C and at a constant pressure of 3.5 MPa. From the experimental results, it is observed that a conversion and/or degree of hydrogenation above 95% was achieved in a single pass from the designed continuous process. This is the first continuous process for HNBR production that gives conversions above 95% till date. Optimum catalyst concentration for a given mean residence time to achieve conversions above 95% were obtained. Finally, a mechanistic model for the SM reactor performance with respect to hydrogenation of NBR was proposed and validated with the obtained experimental results. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2002John Louis-Ugbo The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to two calcium-based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP-2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP-2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera. Differences observed between the two materials for the area under the retention vs. time profile (AUC; 988%day for BCP vs. 1070%day for BCP/ACS, p = 0.57) and the mean residence time (MRT; 10.2 days for BCP vs. 7.6 days for BCP/ACS, p = 0.06) were not statistically significant. Initial retention/incorporation of rhBMP-2 was slightly higher for rhBMP-2/BCP/ACS than for rhBMP-2/BCP (96.8% vs. 86.0%, p lt; 0.05). Animals receiving rhBMP-2/BCP showed a longer terminal retention half-life (t1/2) than did those receiving rhBMP-2/BCP/ACS (7.5 vs. 4.5 days, p < 0.05). The urinary radioactivity recovery data supported the data obtained by scintigraphy. Over the 36 day collection period, essentially complete recovery of radioactivity (dose) in urine was observed for rhBMP-2/BCP and rhBMP-2/BCP/ACS and the majority of the radioactivity (approximately 95%) was soluble in trichloroacetic acid, suggesting extensive catabolism of rhBMP-2 before renal excretion. Fecal recovery of radioactivity was low, approximately 2,3%. In conclusion, rhBMP-2 was retained at the implant site when delivered with either BCP or BCP/ACS based on mean residence time and area under the retention curve vs. time profile. Use of these matrices resulted in detectable rhBMP-2 levels at the surgical site for over a week in contrast to data reported with several other matrices that lasted less time. Systemic catabolism and elimination of the rhBMP-2 was extensive and systemic presence of the protein was negligible. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrinJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006Susan A. Charman Abstract The pharmacokinetic profile and renal clearance of a novel synthetic ozonide antimalarial (1) was found to be significantly altered when intravenously administered to rats as a cyclodextrin-based formulation (0.1 M Captisol®, a sulfobutylether ,-cyclodextrin derivative (SBE7 -,-CD)) compared to a cyclodextrin-free isotonic buffered glucose formulation. There was an 8.5-fold decrease in the steady-state blood volume of distribution, a 6.6-fold decrease in the mean residence time and a greater than 200-fold increase in renal clearance of 1 when administered in the cyclodextrin formulation. Analysis of the whole blood and plasma concentration profiles revealed an essentially constant blood to plasma ratio when 1 was administered in the cyclodextrin-free formulation, whereas this ratio changed as a function of time when administered in the presence of the cyclodextrin derivative. It is postulated that the observed differences were due to a very strong complexation interaction between 1 and the cyclodextrin, resulting in a slow dissociation of the complex in vivo, and altered distribution and excretion profiles. Preliminary studies using isothermal titration calorimetry (ITC) indicated that the association constant for the 1/Captisol® complex was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:256,267, 2006 [source] Volume of distribution at steady state for a linear pharmacokinetic system with peripheral eliminationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2004Leonid M. Berezhkovskiy Abstract The problem of finding the steady-state volume of distribution Vss for a linear pharmacokinetic system with peripheral drug elimination is considered. A commonly used equation Vss,=,(D/AUC)*MRT is applicable only for the systems with central (plasma) drug elimination. The following equation, Vss,=,(D/AUC)*MRTint, was obtained, where AUC is the commonly calculated area under the time curve of the total drug concentration in plasma after intravenous (iv) administration of bolus drug dose, D, and MRTint is the intrinsic mean residence time, which is the average time the drug spends in the body (system) after entering the systemic circulation (plasma). The value of MRTint cannot be found from a drug plasma concentration profile after an iv bolus drug input if a peripheral drug exit occurs. The obtained equation does not contain the assumption of an immediate equilibrium of protein and tissue binding in plasma and organs, and thus incorporates the rates of all possible reactions. If drug exits the system only through central compartment (plasma) and there is an instant equilibrium between bound and unbound drug fractions in plasma, then MRTint becomes equal to MRT,=,AUMC/AUC, which is calculated using the time course of the total drug concentration in plasma after an iv bolus injection. Thus, the obtained equation coincides with the traditional one, Vss,=,(D/AUC)*MRT, if the assumptions for validity of this equation are met. Experimental methods for determining the steady-state volume of distribution and MRTint, as well as the problem of determining whether peripheral drug elimination occurs, are considered. The equation for calculation of the tissue,plasma partition coefficient with the account of peripheral elimination is obtained. The difference between traditionally calculated Vss,=,(D/AUC)*MRT and the true value given by (D/AUC)*MRTint is discussed. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1628,1640, 2004 [source] The pharmacokinetics of antofloxacin in renally impaired ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2008X. Y. Pang Our aim was to investigate whether renal impairment induced by cisplatin altered the pharmacokinetics of antofloxacin. Antofloxacin (7.5 mg kg,1, i.v.) was given to normal or renally impaired rats (induced by cisplatin). Concentrations of antofloxacin in plasma and urine were measured using HPLC. Pharmacokinetic parameters were estimated. The plasma concentrations of antofloxacin in the renally impaired rats were significantly higher than those in the normal rats, accompanied by significant increase of the area under the plasma concentration-time curve (AUC) (968.78 ± 259.39 ,g min mL,1 versus 509.84 ± 46.19 ,g min mL,1 in normal rats P < 0.05). The system clearance (CL) and renal clearance (CLR) of antofloxacin decreased from 12.66 ± 1.15 mL kg,1 min,1 and 3.21 ± 1.80 mLkg,1 min,1 in normal rats, to 6.63 ± 2.82 mLkg,1 min,1 and 0.31 ± 0.15 mLkg,1 min,1, respectively. No differences between two treatments in half-life and mean residence time were found. We concluded that renal impairment induced by cisplatin significantly altered the pharmacokinetics of antofloxacin and resulted in decrease of the renal elimination. [source] Contradistinction between doxorubicin and epirubicin: in-vivo metabolism, pharmacokinetics and toxicodynamics after single- and multiple-dosing in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2001Sandhya Ramanathan-Girish There is compelling in-vitro evidence that the evaluation of doxorubicin or epirubicin pharmacokinetics based solely on plasma concentration may not fully elucidate the differences between the two drugs. Both compounds bind to erythrocytes and their different binding to haemoglobin may influence their disposition in the body. The purpose of the present study was to compare the pharmacokinetics and metabolism of doxorubicin and epirubicin based on the plasma concentration, amount associated with blood cells and simultaneous monitoring of biliary and urinary elimination of unchanged drug and metabolites after single- and multiple-dose injections. The level of sarcoplasmic reticulum Ca2+ ATPase in the heart was also measured as a biomarker of cardiotoxicity. Male Sprague-Dawley rats were treated in a parallel design with doxorubicin or epirubicin on a multiple-dosing basis (4 mg kg,1 per week) or as a single dose injection (20 mg kg,1). Blood, urine and bile samples were collected periodically after each dose in the multiple-dosing regimen and the single dose injection, and at the end of each experiment the hearts were removed. The concentrations of each drug in plasma, blood cells, bile and urine samples were determined, and by simultaneous curve-fitting of plasma and bile data according to compartmental analysis, the pharmacokinetic parameters and constants were estimated. The concentration of drug associated with blood cells was analysed according to non-compartmental analysis. The bile and urine samples provided the in-vivo metabolic data. The level of Ca2+ ATPase in the heart, determined by Western blotting, was used as the toxicodynamic parameter to correlate with the kinetic data. Multiple-dosing regimens reduced the total plasma clearance and increased the area under the plasma concentration-time curve of both drugs. Also, the area under the curve of doxorubicin associated with blood cells increased with the weekly doses, and the related mean residence time (MRT) and apparent volume of distribution (Vdss) were steadily reduced. In contrast to doxorubicin, the MRT and Vdss of epirubicin increased significantly. Metabolic data indicated significant differences in the level of alcohol and aglycones metabolites. Doxorubicinol and doxorubicin aglycones were significantly greater than epirubicinol and epirubicin aglycone, whereas epirubicinol aglycone was greater than doxorubicinol aglycone. The area under the blood cells concentration-time curve correlated linearly with the changes in Ca2+ ATPase net intensity. The results of this study demonstrate the importance of the kinetics of epirubicin and doxorubicin associated with blood cells. Linear correlation between the reduction of net intensity of the biomarker with the area under the curve of doxorubicin associated with blood cells confirms that the differences between the two compounds are related to their interaction with blood cells. This observation together with the observed differences in metabolism may underline a significant role for blood cells in distribution and metabolism of doxorubicin and epirubicin. [source] A novel and simple type of liposome carrier for recombinant interleukin-2JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2001Eri Kanaoka The strong interaction between recombinant interleukin-2 (IL-2) and liposome was characterized and its possible application to drug-delivery control considered. The liposomes were prepared with egg phosphatidylcholine, distearoyl-phosphatidylglycerol (DSPG), dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylglycerol or distearoyl-phosphatidylcholine (DSPC). Small and hydrophobic liposomes were selected, which were composed of saturated and long-fatty-acid-chain phospholipids. When the composition and the mixture ratio of IL-2 and the liposome were optimized, more than 95% of the lyophilized IL-2 (Imunace, 350000, JRU) was adsorbed consistently onto the DSPC-DSPG liposome (molar ratio, 10:1; 25 ,mol mL,1; 30 nm in size). Merely mixing IL-2 lyophilized with liposome suspension is convenient pharmaceutically. After intravenous administration to mice, liposomal IL-2 was eliminated half as slowly from the systemic circulation as free IL-2, with more than 13 and 18 times more IL-2 being delivered to the liver and spleen, respectively. After subcutaneous administration of liposomal IL-2 to mice, the mean residence time of IL-2 in the systemic circulation was 8 times that of free IL-2. These results show that IL-2 consistently adsorbs onto the surface of liposomes after optimization of its composition and mixing ratio. Intravenous and subcutaneous administration to mice demonstrates the gradual release of IL-2. Further trials are warranted using these liposomes. [source] The Effect of Different Dosing Schedules of UCN-01 on its Pharmacokinetics and Cardiohaemodynamics in DogsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2000N. KURATA 7-Hydroxy-staurosporine (UCN-01) is now under development as a novel anticancer drug. In clinical studies, different infusion schedules are being investigated in the USA and Japan. To examine the effect of different infusion schedules on the pharmacokinetics and cardiohaemodynamics of UCN-01, dogs were treated with UCN-01 as either a 3-h or a 24-h constant intravenous infusion. Blood pressure and heart rate, together with UCN-01 concentrations during and after infusion, were monitored. To analyse the relationship between the pharmacokinetics and cardiohaemodynamics of UCN-01, the plasma concentration of UCN-01 at the end of infusion (Cend), the area under the plasma concentration versus time curves (AUC0-,) and the mean residence time (MRT) were used. As indices of cardiohaemodynamic changes, the area under decreasing systolic blood pressure and increasing heart rate versus time curves (dAUCpressure and AUCheart rate) were calculated by the trapezoidal method. For the 3-h (0.22 and 0.65 mgkg,1) and 24-h infusion (0.81 to 6.48 mgkg,1), systolic and diastolic blood pressures fell after or during infusions, accompanied by a dose-dependent increase in heart rate for both infusions. During both infusion schedules, the plasma concentrations of UCN-01 gradually increased and Cend showed a dose-proportional increase. After that, UCN-01 was eliminated bi-exponentially with an elimination half-life of 5.14 ± 1.12 to 8.32 ± 1.80 h. The total clearance (CLtotal) ranged from 0.383 to 0.666 ± 0.149L h,1kg,1. There was no significant difference in these parameters among the doses in each infusion schedule, indicating that UCN-01 has a linear pharmacokinetic profile over the dose range examined for each infusion, and there were also no significant differences between the 3-h and 24-h infusion except for MRT. The pharmacokinetic parameters of Cend, AUC0-, and slope0-3h exhibited a degree of correlation with the AUCheart rate in the 3-h infusion and correlated significantly with the dAUCpressure in the 24-h infusion. The MRT did not correlate with cardiohaemodynamic changes during either infusion. In conclusion, the pharmacokinetic profile of UCN-01 after the shorter infusion is similar to that after the longer one. However, a longer dosing period of UCN-01 increased the residence time in comparison with the shorter infusion. This may be due to the effect on the circulatory function in dogs. [source] SIAM-Like Phenomenon Caused by Low Doses of AlcoholALCOHOLISM, Issue 2010Akiko Shimamoto Background:, Swift increase in alcohol metabolism (SIAM) is usually evoked by a large dose of ethanol, which is often demonstrated by an abrupt increase in oxygen uptake. SIAM was induced by low doses of ethanol and evaluated by pharmacokinetic analyses of ethanol and its metabolites. Methods:, Rabbits were initially administered 1.0 g/kg of ethanol solution and the same dose was given to the bolus group 6 hours after the first injection. The infusion group was administered 0.25 g/kg/h of ethanol 2 hours after the first injection. Blood concentrations of ethanol, acetaldehyde, and acetate were then determined and comparisons were made using pharmacokinetic parameters. Results:, A significantly higher ethanol elimination rate was observed after re-administration of ethanol to the bolus group. Other pharmacokinetic parameters were unaffected. The concentration at steady state (Css) for the infusion group was stable. A significantly higher level of mean residence time (MRT) in blood acetaldehyde was observed for the bolus group, whereas no MRT changes were observed for the infusion group. A significantly higher level of blood acetate Css was observed after re-administration of ethanol to the bolus group, following the changes in area under concentration and MRT. No Css changes were observed for the infusion group. The Css of acetate at stage 2 was significantly higher for the bolus group, compared to the infusion group. Conclusion:, Low doses of ethanol enhanced alcohol metabolism in rabbits, according to a pharmacokinetic analysis of circulating ethanol concentrations. Simultaneous analyses of its metabolites followed the kinetic of ethanol. [source] A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standardsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2003M. Morfini Summary., When the one-stage clotting assay is used in comparison with the chromogenic and immunological assays, plasma levels of factor (F)VIII are underestimated by 40,50% after infusion of B-domain deleted recombinant FVIII (BDD-rFVIII) in patients with hemophilia. A possible way to counteract the underestimation of FVIII levels by the one-stage assay is the adoption of a recombinant FVIII reference standard instead of a plasma standard. To evaluate the usefulness of such a standard [ReFacto® Laboratory Standard (RLS)], the pharmacokinetic parameters of a single dose of BDD-rFVIII (25 U kg,1) were evaluated in a multicenter study carried out in 18 patients with severe hemophilia A. The very low in vivo recovery, obtained with the combination of the one-stage assay and plasma reference standard, was increased up to the values obtained by the chromogenic assay when the results were expressed in terms of RLS. When the plasma standard was used, the one-stage/chromogenic ratio was 0.82 ± 0.12 for FVIII levels above 25 U dL,1 and 1.42 ± 0.99 for FVIII levels below 25 U dL,1. Using the RLS, the one-stage/chromogenic ratio increased to 1.01 ± 0.19 at FVIII levels above 25 U dL,1, as a consequence of a complete overlap of the two decays; however, at FVIII levels below 25 U dL,1, the one-stage/chromogenic ratio was still 1.6 ± 0.85. After the twelfth hour, FVIII concentrations obtained by chromogenic assay were always lower than those resulting from the one-stage clotting assay, independently of the standard used. Results obtained by chromogenic assay were not affected by the type of standard used. Compared with those obtained by the one-stage assay, higher values of clearance, lower volume of distribution area and shorter plasma half-life or mean residence time were obtained by chromogenic assay because of a shape change of the decay curve due to a shift to higher values in the first part (time interval 0,12 h) and to lower values in the second part of the decay curve (time interval 12,48 h). As a consequence, the slope of the decay curve obtained by means of chromogenic assay was steeper. In conclusion, the more homogeneous results of in vivo recovery and pharmacokinetic analysis, due to the decrease of discrepancy between the two methods when RLS was used, make the cheaper and more widely used one-stage assay preferable to the more expensive chromogenic assay, on condition that the ReFacto specific standard has used. [source] Pharmacokinetics of ketamine in plasma and milk of mature Holstein cowsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010G. SELLERS Sellers, G., Lin, H. C., G. Riddell, M. G., Ravis, W. R., Lin, Y. J., Duran, S. H., Givens, M.D. Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows. J. vet. Pharmacol. Therap. 33, 480,484. The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasma Tmax was 0.083 h and plasma Cmax was 18 135 ± 22 720 ng/mL. Plasma AUC was 4484 ± 1,398 ng·h/mL. Plasma t½, was 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady-state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. Milk Tmax was detected at 0.67 ± 0.26 h with Cmax of 2495 ± 904 ng/mL. Milk AUC till the last time was 6593 ± 2617 ng·h/mL with mean AUC milk to AUC plasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL. [source]
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