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  • pharmacokinetics  (2,025)
  • Rat  (826)
  • phosphorus  (681)
  • Inversion
  • Springer  (3,567)
  • American Geophysical Union  (2)
  • Institut für Meteorologie und Geophysik  (2)
  • Wiley  (2)
  • 3  (1)
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  • 1
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    Moist synoptic transport of CO2 along the mid-latitude storm track (2011)
    American Geophysical Union
    Details
    Publication Date: 2022-05-25
    Description: Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 38 (2011): L09804, doi:10.1029/2011GL047238.
    Description: Atmospheric mixing ratios of CO2 are strongly seasonal in the Arctic due to mid-latitude transport. Here we analyze the seasonal influence of moist synoptic storms by diagnosing CO2 transport from a global model on moist isentropes (to represent parcel trajectories through stormtracks) and parsing transport into eddy and mean components. During winter when northern plants respire, warm moist air, high in CO2, is swept poleward into the polar vortex, while cold dry air, low in CO2, that had been transported into the polar vortex earlier in the year is swept equatorward. Eddies reduce seasonality in mid-latitudes by ∼50% of NEE (∼100% of fossil fuel) while amplifying seasonality at high latitudes. Transport along stormtracks is correlated with rising, moist, cloudy air, which systematically hides this CO2 transport from satellites. We recommend that (1) regional inversions carefully account for meridional transport and (2) inversion models represent moist and frontal processes with high fidelity.
    Description: This research is supported by the National Aeronautics and Space Administration contracts NNX08AT77G, NNX06AC75G, and NNX08AM56G.
    Keywords: Atmospheric transport ; Carbon cycle ; Inversion ; Isentropic coordinates ; Synoptic weather ; Tracer modeling
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 2
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    A box model test of the freshwater forcing hypothesis of abrupt climate change and the physics governing ocean stability (2011)
    American Geophysical Union
    Details
    Publication Date: 2022-05-26
    Description: Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 25 (2010): PA4222, doi:10.1029/2010PA001936.
    Description: Observations and an ocean box model are combined in order to test the adequacy of the freshwater forcing hypothesis to explain abrupt climate change given the uncertainties in the parameterization of vertical buoyancy transport in the ocean. The combination is carried out using Bayesian stochastic inversion, which allows us to infer changes in the mass balance of Northern Hemisphere (NH) ice sheets and in the meridional transports of mass and heat in the Atlantic Ocean that would be required to explain Dansgaard-Oeschger Interstadials (DOIs) from 30 to 39 kyr B.P. The mean sea level changes implied by changes in NH ice sheet mass balance agree in amplitude and timing with reconstructions from the geologic record, which gives some support to the freshwater forcing hypothesis. The inversion suggests that the duration of the DOIs should be directly related to the growth of land ice. Our results are unaffected by uncertainties in the representation of vertical buoyancy transport in the ocean. However, the solutions are sensitive to assumptions about physical processes at polar latitudes.
    Description: This material is based upon work supported by the National Science Foundation under grant OCE‐0402363 and Department of Energy grant DE‐FG02‐08ER64619.
    Keywords: Inversion ; MOC ; Abrupt ; Sea level ; Coral ; Mixing
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/postscript
    Format: application/pdf
    Format: text/plain
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  • 3
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    Tortonian-Pleistocenic oceanic features in the Southern Tyrrhenian Sea: magnetic inverse model of the Selli-Vavilov region (2009)
    Springer
    Details
    Publication Date: 2017-04-04
    Description: We show the magnetic model of the Selli-Vavilov region. The Selli Line is known as the northwestern edge of the southern Tyrrhenian basin. The tectonic evolution of the Tyrrhenian basin is dominated by a Tortonian - Quaternary extension through the eastward movement of the Apennine subduction system. This migration has generated a diffuse stretching of the continental crust with the emplacement of new oceanic material. This latter occurred in several localized zones where the eastward retreating of the Ionian subduction system produced a strong depletion of the crust with formation of basins and correlated spreading. Nowadays the presence of oceanic crust is confirmed through direct drilling investigation but a complete mapping of the oceanic crustal distribution is still lacking. The Selli-Vavilov region shows a differentiated crustal setting where seamount structures, the oceanic basement portions and continental crust blocks are superimposed. To this aim, a 2D inversion of the magnetic data of this region was conducted to define buried structures. The magnetic susceptibility pattern was computed by solving the least squares problem of the misfit between the predicted and real data for separated wavebands. This method produced two 2D models of the high and low frequency fields of the Selli-Vavilov region. The two apparent susceptibility maps provide different information for distinct ranges of depth. The results of the inversions were also combined with seismic data of the Selli region highlighting the position of the highly-magnetized buried bodies. The results confirm a role for the Selli Line as a deep crustal boundary dividing the Sardinian passive domain from the easternmost active region where different oceanic structures are located. The Selli Line has worked as a detachment fault system which has moved eastward. Finally, the Selli-Vavilov region may be interpreted as a tectonic result due to a passive asymmetrical rift occurred between the Tortonian and Pliocene.
    Description: Published
    Description: 251-266
    Description: 2.6. TTC - Laboratorio di gravimetria, magnetismo ed elettromagnetismo in aree attive
    Description: 3.4. Geomagnetismo
    Description: 3.5. Geologia e storia dei sistemi vulcanici
    Description: JCR Journal
    Description: reserved
    Keywords: Geomagnetism ; Tectonics ; Geodynamics ; Inversion ; Oceanic crust ; Volcanic structure ; 04. Solid Earth::04.05. Geomagnetism::04.05.04. Magnetic anomalies ; 04. Solid Earth::04.07. Tectonophysics::04.07.02. Geodynamics ; 05. General::05.01. Computational geophysics::05.01.03. Inverse methods
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 4
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    Automatic versus manual model differentiation to compute sensitivities and solve non-linear inverse problems (2002)
    3
    In:  Computers and Geosciences, Münster, 3, vol. 28, no. 45, pp. 309-326, pp. L11609, (ISBN 0-471-26610-8)
    Details
    Publication Date: 2002
    Keywords: Inversion ; Data analysis / ~ processing ; Non-linear effects ; Discrimination ; C&G
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    BIBLIOGRAPHY SEISMOLOGY
  • 5
    Electronic Resource
    Electronic Resource
    Kegelschnittbüschel und Inversion (2000)
    Springer
    Geometriae dedicata 83 (2000), S. 31-37 
    Details
    ISSN: 1572-9168
    Keywords: Vollständiges Viereck ; Kegelschnittbüschel ; Konjugiertheitsabbildung ; Inversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract The conjugacy mapping rel. to a complete quadrangle in a Pappian projective plane of characteristic ≠2 is constructed by using a bijection of the line set onto the bundle of conics through the diagonal points of the quadrangle. The inversion with center O of the inversion circle going through the point P in the Euclidean plane proves to be the product of the reflection at OP and the affine restriction of the conjugacy mapping rel. to the quadrangle having P as one of its vertices and O together with the circular points at infinity as diagonal points.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005294714649
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  • 6
    Electronic Resource
    Electronic Resource
    Nutrient flows and land use change in a rural catchment: a modelling approach (2000)
    Springer
    Landscape ecology 15 (2000), S. 187-199 
    Details
    ISSN: 1572-9761
    Keywords: BOD5 ; catchment ; empirical model ; land use change ; land use scenarios ; nitrogen ; phosphorus ; runoff ; SO4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Due largely to unprecedented land-use changes in the Porijõgi River catchment (southern Estonia) losses of nutrients and organic matter have decreased significantly. During the period 1987–1997 abandoned lands increased from 1.7 to 10.5% and arable lands decreased from 41.8 to 23.9%. At the same time, the runoff of total-N, total-P, SO4 and organic matter (after BOD5) decreased from 25.9 to 5.1, 0.32 to 0.13, 78 to 48, and 7.4 to 3.5 kg ha−1 yr−1, respectively. The most significant decreases occurred in agricultural subcatchments while the changes were insignificant in the forested upper course catchment. A simple empirical model which incorporates land-use pattern, fertilization intensity, soil parameters and water discharge accurately described the variations of total-N and total-P runoff in both the whole catchment and its agricultural subcatchments (R 2 varies from 0.95–0.99 for N to 0.49–0.93 for P). In small agricultural subcatchments the rate of fertilization is found the most important factor for nitrogen runoff, whereas in larger mosaic watersheds land use pattern plays the main role. Seven alternative scenarios compiled on the base of the empirical model allow to forecast potential nitrogen and phosphorus losses from the catchment. This information can be used in further landscape and regional planning of the whole region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008181811552
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  • 7
    Electronic Resource
    Electronic Resource
    DC-resistivity mapping of internal landfill structures: two pre-excavation surveys (2000)
    Springer
    Environmental geology 39 (2000), S. 360-371 
    Details
    ISSN: 1432-0495
    Keywords: Key words Environmental geophysics ; Resistivity ; Inversion ; Landfill mining ; Waste ; Characterization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract  Geophysical investigations using 2-D DC resistivity were carried out on old parts of two similar landfills, with waste of different ages. The data sets, which included high data density in both vertical and horizontal directions, were interpreted with 2-D smoothness constrained inversion. The landfills were excavated after the surveying. The objective was to test the capability of the resistivity method as a pre-characterization technique. The objectives were only partially fulfilled. First, the moisture content was the parameter that appeared to exert the dominant control over the resistivity distribution of the landfill. The most important potential information that can be recovered is, therefore, an indication of the waste piles hydraulics. Second, it was neither possible to estimate the amount of recoverable soils, nor to correlate the type of waste with the resistivity models. However, discrete anomalies were identified, and if specific materials are searched for, the resistivity models indicate possible places to search.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002540050015
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  • 8
    Electronic Resource
    Electronic Resource
    A polymorphism of the rat T-cell receptor β-chain variable gene 13 (BV13S1) correlates with the frequency of BV13S1-positive CD4 cells (2000)
    Springer
    Immunogenetics 51 (2000), S. 296-305 
    Details
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050623
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  • 9
    Electronic Resource
    Electronic Resource
    Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat (2000)
    Springer
    Histochemistry and cell biology 122 (2000), S. 507-517 
    Details
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00418-004-0708-7
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  • 10
    Electronic Resource
    Electronic Resource
    Thermal Destruction of Polydimethyl-Siloxane on a Phosphorus-containing Silica Surface (2000)
    Springer
    Journal of thermal analysis and calorimetry 62 (2000), S. 335-344 
    Details
    ISSN: 1572-8943
    Keywords: phosphorus ; polydimethylsiloxane ; silica ; surface ; thermogravimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Thermogravimetry, differential thermal analysis, and IR spectroscopy were used to investigate the process of thermal destruction of adsorbed polydimethylsiloxane (PDMS) in air. The disperse adsorbents were pristine fumed silica and modified fumed silica whose surface contained oxygen compounds of phosphorus. It was shown that under the given experimental conditions the thermal destruction of PDMS on the fumed silica surface was accompanied by the complete transformation of the adsorbed PDMS to SiO2. In the case of phosphorus-containing silica, the thermal destruction proceeded in a different way. It was found that at 140–300°C depolymerization of the siloxane chains of a certain part of the adsorbed polymer took place with the concurrent removal of volatile products of the reaction. However, the remaining part of the adsorbed PDMS interacted with the modified silica surface to form chemisorbed dimethylsilyl structures. The thermal destruction of the chemisorbed fragments of PDMS in air was initiated at 400°C or above for both types of silica investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1010184519492
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  • 11
    Electronic Resource
    Electronic Resource
    XRD Investigations of the Phosphorus Effect on the Oxidation of TiAl Alloys by High-Resolution Methods (2000)
    Springer
    Oxidation of metals 54 (2000), S. 317-337 
    Details
    ISSN: 1573-4889
    Keywords: TiAl ; oxidation ; phosphorus ; microdiffraction ; doping ; rutile
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Recently it has been found that very small amounts (a few 100 ppm) of Padded to γ -titanium aluminide can significantly alter the oxidationbehavior between 973 and 1273 K. The mechanism responsible for this changeis, however, still not clear. In the present study, phosphorus wasincorporated into the surface of TiAl (containing 50 at.% Al) by ionimplantation and oxidation tests were carried out at 1173 K inair. Improvement of oxidation resistance is only temporary up to 100 hr forphosphorus-implanted TiAl. After 100 hr, the oxidation rate increases andbreakaway oxidation follows. XRD and EPMA showed that the breakawayoxidation is connected with massive nitride formation. Two different modelsare proposed which can explain the effect of phosphorus additions on theoxidation kinetics of TiAl during the protective stage within the first100 hr. The breakaway effect can be explained by penetration of air to themetal–oxide interface zone because of microcrack formation in theoxide scale, which was experimentally proved by acoustic-emission analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004606513758
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  • 12
    Electronic Resource
    Electronic Resource
    Vanadium–molybdenum phosphates supported by TiO2 for ethane oxidation to acetic acid: a correlation between the local environment of vanadium and the reactivity (2000)
    Springer
    Topics in catalysis 11-12 (2000), S. 101-109 
    Details
    ISSN: 1572-9028
    Keywords: ethane ; vanadium ; molybdenum ; phosphorus ; titanium oxide ; acetic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Different complementary physicochemical tools have been used to explain the improvement of the catalytic performances for ethane oxidation into acetic acid induced by the addition of molybdenum as phosphate to vanadium phosphate deposited on TiO2-anatase, at a coverage below the monolayer. Electron microscopy techniques have shown that the elements are dispersed on the support. Electron spin resonance, laser Raman and UV-visible spectroscopies have evidenced that the short range order around vanadium is modified by the presence of molybdenum. 51V NMR has shown that molybdenum favours the octahedral symmetry of vanadium. The acidic properties of the catalyst are improved by the adding effect of molybdenum and by the addition of water. This should explain a better desorption of acetic acid and the improvement of the corresponding yield. This confirms the importance of the atomic environment of vanadium-based oxides to control the mild oxidation of light alkanes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1027223208829
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  • 13
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    Pharmacology of Fluorinated Pyrimidines: Eniluracil (2000)
    Springer
    Investigational new drugs 18 (2000), S. 373-381 
    Details
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006453500629
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  • 14
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    Sources, sinks, and fluxes of nutrients (N + P) in a small highly modified urban estuary in southern California (2000)
    Springer
    Urban ecosystems 4 (2000), S. 125-144 
    Details
    ISSN: 1573-1642
    Keywords: nitrogen ; phosphorus ; macroalgae ; estuary ; anthropogenic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Our objective was to begin to investigate sources, sinks, and flux rates of nitrogen (N) and phosphorus (P) in Famosa Slough, a small (12 ha) highly modified urban estuary in San Diego, California, U.S.A. The hydrology of Famosa Slough has been modified by culverts that dampen tidal influence and seasonal runoff from two urban watersheds, each of which has been implicated as a nutrient source that generates nuisance algal blooms. In 1995 and 1996, the ranges of nutrients measured in the water column were extremely wide; upper values exceeded those in other estuaries identified as eutrophic. Average dissolved inorganic nitrogen ranged from 2 to 250 μM, while dissolved inorganic phosphorus ranged from 〈1 to 15 μM. Nutrient content of the water changed rapidly both spatially and temporally depending on the tides and rainfall. While tidal water dominated this system, especially in the dry season, our results indicate that Famosa Slough's small watershed, not the larger watershed of the San Diego River, was the major source of nutrients during rainfall. Sediment nutrients were also high (∼3 mg N g dry wt−1 and 0.600 mg P g dry wt−1). Short-term flux studies suggest that the large accumulations of opportunistic green macroalgae commonly found in this estuary, and possibly the sediments, may act as a large and rapid sink for nutrients during times of high nutrient supply. We suggest that small, shallow estuaries in urban settings may have more complex and rapid nutrient dynamics than those found in larger systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011359311384
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  • 15
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    Co-development of wetland soils and benthic invertebrate communities following salt marsh creation (2000)
    Springer
    Wetlands ecology and management 8 (2000), S. 197-207 
    Details
    ISSN: 1572-9834
    Keywords: benthic invertebrates ; mitigation ; nitrogen ; organic matter ; pedogenesis ; phosphorus ; plant productivity ; restoration and rehabilitation ; salt marsh ; wetland creation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The development of wetland soil characteristics andbenthic invertebrate communities were evaluated increated Spartina alterniflorasalt marshes inNorth Carolina ranging in age from 1 to 25 years-old.A combination of measurements from different-agecreated marshes as well as periodic measurements overtime on two marshes were used to (1) document rates ofwetland pedogenesis, especially soil organic matter,and, (2) explore relationships between soil andbenthic invertebrate community development. Soilmacro-organic matter (MOM, the living and dead rootand rhizome mat), organic C and N increased and bulkdensity decreased during the 25 years following marshestablishment. The most dramatic changes in bulkdensity, MOM, C and N occurred within the upper 10 cmof the soil with lesser changes below this depth.Created marshes were sinks for organic C (90–140g·m-2·yr-1) and N (7–11g·m-2·yr-1) but not for P (0–1g·m-2·yr-1). The density of benthicinvertebrates (〉250 μm) and subsurface-depositfeeding oligochaetes also increased over time oncreated salt marshes. Invertebrate and oligochaetedensity were strongly related to MOM content(r2= 0.83–0.87) and soil organic C(r2= 0.52–0.82) and N (r2= 0.62–0.84). Thesefindings suggest that, in created salt marshes,development of the benthic invertebrate community istied to marsh soil formation, especially accumulationof organic matter as MOM and soil. Field studies thatmanipulate the quantity and quality of soil organicmatter are needed to elucidate the relationshipbetween salt marsh pedogenesis and benthicinvertebrate community development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008448620605
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  • 16
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    Allometric Pharmacokinetic Scaling: Towards the Prediction of Human Oral Pharmacokinetics (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 410-418 
    Details
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007520818956
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  • 17
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    In Vivo Absorption Properties of Orally Administered Recombinant Human Interleukin-11 (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 482-485 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007545524408
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  • 18
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    New Insights into the Pharmacokinetics and Metabolism of (R,S)-Ifosfamide in Cancer Patients Using a Population Pharmacokinetic-Metabolism Model (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 645-652 
    Details
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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    URL: http://dx.doi.org/10.1023/A:1007561727948
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    Pharmacokinetics and Antitumor Effect of Doxorubicin Carried by Stealth and Remote Loading Proliposome (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 782-787 
    Details
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007543805947
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    Pharmacokinetic-Pharmacodynamic Modelling of Morphine Transport Across the Blood-Brain Barrier as a Cause of the Antinociceptive Effect Delay in Rats—A Microdialysis Study (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1220-1227 
    Details
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026414713509
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    Confidence Interval Criteria for Assessment of Dose Proportionality (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1278-1283 
    Details
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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    URL: http://dx.doi.org/10.1023/A:1026451721686
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    Pharmacokinetics of a Hematoregulatory Peptide (SK&F 107647) in Healthy Male Volunteers and in Patients with Colorectal or Pancreatic Adenocarcinoma Not Amenable to Standard Therapy (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 385-390 
    Details
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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    URL: http://dx.doi.org/10.1023/A:1007512617139
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    A Human Physiologically-Based Model for Glycyrrhzic Acid, A Compound Subject to Presystemic Metabolism and Enterohepatic Cycling (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1516-1525 
    Details
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
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    URL: http://dx.doi.org/10.1023/A:1007661209921
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    Population Pharmacokinetic/ Pharmacodynamic Modeling of Cetrorelix, a Novel LH-RH Antagonist, and Testosterone in Rats and Dogs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 328-335 
    Details
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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    URL: http://dx.doi.org/10.1023/A:1007557207590
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    Bioequivalence of Methylphenidate Immediate-Release Tablets Using a Replicated Study Design to Characterize Intrasubject Variability (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 381-384 
    Details
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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    URL: http://dx.doi.org/10.1023/A:1007560500301
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    In Vivo Specific Binding Characteristics and Pharmacokinetics of a 1,4-Dihydropyridine Calcium Channel Antagonist in the Senescent Mouse Brain (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 844-850 
    Details
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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    URL: http://dx.doi.org/10.1023/A:1007512426420
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    Potential Role of P-Glycoprotein in Affecting Hepatic Metabolism of Drugs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 903-905 
    Details
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007570517183
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    An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    Details
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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    URL: http://dx.doi.org/10.1023/A:1007500910566
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    Physiological Modeling of Altered Pharmacokinetics of a Novel Anticancer Drug, UCN-01 (7-Hydroxystaurosporine), Caused by Slow Dissociation of UCN-01 from Human α1-Acid Glycoprotein (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 553-564 
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    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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    URL: http://dx.doi.org/10.1023/A:1007512832006
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    Influence of Stereoselective Pharmacokinetics in the Development and Predictability of an IVIVC for the Enantiomers of Metoprolol Tartrate (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1019-1025 
    Details
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
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    Modulation of Paired-Pulse Responses in the Dentate Gyrus: Effects of Normal Maturation and Vigilance State (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 128-134 
    Details
    ISSN: 1573-9686
    Keywords: Hippocampus ; Vigilance states ; Paired-pulse ; Dentate gyrus ; Dentate granule cells ; Evoked response ; Rat ; In vivo studies ; Perforant path ; Maturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract This study examined the effect of normal development and vigilance state on the modulation of dentate granule cell activity in the freely moving rat at 15, 30, and 90 days of age across three vigilance states: quiet waking, slow-wave sleep, and rapid eye movement sleep. Using paired-pulse stimulation, the paired-pulse index (PPI) was obtained for the dentate evoked field potentials elicited by the stimulation of the medial perforant path. Although significant differences in PPI values were observed during development, no significant vigilance state related changes were obtained. Preweaning infant rats, i.e., 15-day old, exhibited significantly less early (interpulse intervals, IPI= 20–50 ms) and late (IPI = 300–1000 ms) inhibition, and less facilitation (IPI = 50–150 ms) when compared to the 90-day old adult rats during all three vigilance states. PPI values obtained from the 30-day old group fell intermediate between the 15- and 90-day old animals. These changes in PPI values provide a quantitative measure of changes in the modulation of dentate granule cell excitability during normal maturation. They can now can be used to evaluate the impact of various insults, such as prenatal protein malnutrition or neonatal stress, on hippocampal development. © 2000 Biomedical Engineering Society. PAC00: 8717Nn, 8719La, 8719Nn
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    Left Ventricular Contractility is Impaired Following Myocardial Infarction in the Pig and Rat: Assessment by the End Systolic Pressure–Volume Relation Using a Single-Beat Estimation Technique and Cine Magnetic Resonance Imaging (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 484-494 
    Details
    ISSN: 1573-9686
    Keywords: Heart ; Left ventricle ; LV contractility ; ESPVR ; Pig ; Rat ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The end systolic pressure–volume relation (ESPVR) has been shown to be a relatively load independent measure of left ventricular (LV) contractility. Recently, several single-beat ESPVR computation methods have been developed, enabling the quantification of LV contractility without the need to alter vascular loading conditions on the heart. Using a single-beat ESPVR method, which has been validated previously in humans and assumes that normalized elastance is constant between individuals of a species, we studied the effects of myocardial infarction on LV contractility in two species, the rat and the pig. In our studies, LV pressure was acquired invasively and LV volume determined noninvasively with magnetic resonance imaging, at one week postinfarction in pigs and at 12 weeks postinfarction in rats. Normalized systolic elastance curves in both animal species were not statistically different from that of humans. Also, the slope of the ESPVR $$\left( {E_{es} } \right)$$ decreased significantly following infarction in both species, while the volume-axis intercept $$\left( {V_0 } \right)$$ was unaffected. These results indicate that a single-beat ESPVR method can be used to measure the inotropic response of the heart to myocardial infarction, and that the basis for this method (i.e., constant normalized elastance) is applicable to a variety of mammalian species. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8761Lh, 8719Hh, 8719Rr, 8719Ff
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    Quantifying Coevolution of Nonstationary Biomedical Signals Using Time-Varying Phase Spectra (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 1101-1115 
    Details
    ISSN: 1573-9686
    Keywords: Time–frequency analysis ; Coherence ; Cross correlation ; Nonstationary persistent signals ; Central pattern generator ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We present a novel time-varying phase spectrum (TVPS) method to quantify the dynamics of coevolution of two persistent nonstationary coupled signals. Based on the TVPS, an instantaneous intersignal phase shift is defined within the primary frequency range in which the two signals are highly correlated. The TVPS is estimated using a fixed-window method or an adaptive-window method. In the latter method, the window length changes dynamically and automatically as a function of change in frequency of the signals. The effects of altering window types and lengths on the accuracy of the estimation of the primary phase shift is assessed by analyzing synthesized linear chirp signals with decaying amplitude and constant relative phase shift or decaying amplitude and changing relative phase shifts. The methods developed are also used for determining the evolution of the primary phase shift among ventral root activities during fictive locomotion in an in vitro rat spinal cord preparation. The analyses indicate that the TVPS method in conjunction with the determination of the primary frequency range, allows determination of both the evolution of the coupling strength and the evolution of the phase shift between two persistent nonstationary rhythmic signals in the joint time–frequency domain. An adaptive window reduces the estimation bias and the estimation variability. © 2000 Biomedical Engineering Society. PAC00: 0230-f, 8780Tq
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    URL: http://dx.doi.org/10.1114/1.1313775
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    Growth analysis of maize field crops under phosphorus deficiency (2000)
    Springer
    Plant and soil 223 (2000), S. 119-132 
    Details
    ISSN: 1573-5036
    Keywords: leaf area index ; leaf elongation rate ; phosphorus ; phyllochron ; Zea mays L
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Biomass accumulation by crops depends both on light interception by leaves and on the efficiency with which the intercepted light is used to produce dry matter. Our aim was to identify which of these processes were affected for maize (Zea Mays L., cv Volga) field crops grown under phosphorus (P) deficiency, and assess their relative importance. In this paper, the effects of P deficiency on leaf appearance, leaf elongation rate, final individual leaf area and leaf senescence were studied. The experimental work was carried out in 1995–1977 on a long-term P fertilisation trial located on a sandy soil in the south-west of France. Three P fertilisation regimes have been applied since 1972: no-P (P0 treatment) and different rates of P fertiliser (P1.5:1.5 times the grain P export and P3:3 times the grain P export). These fertilisation regimes have led to contrasted levels of soil P supply, with the P0 treatment being limiting for growth. Very few differences were observed about leaf growth between the P1.5 and P3 treatments. Conversely, the leaf area index (LAI) was significantly reduced in the P0 treatment, especially during the first phases of the crop cycle (up to −60% between the 7- and 14-visible leaves). This effect gradually decreased over time. The lower LAI in P0 treatment was due to two main processes affecting the leaf growth. The final number of leaves per plant and leaf senescence were only slightly modified by P deficiency. Conversely, leaf appearance was delayed during the period between leaf 4 and leaf 9. The value of the phyllochron increased from 47 °C days in the P1.5 treatment to 65 °C days in the P0 treatment. Leaf elongation rates during the quasi-linear phase of leaf expansion were significantly reduced for lower leaves of P0 plants. The final size of leaves L2–L12 was reduced. On the opposite, leaf elongation duration was not greatly affected by P treatments. Before the emergence of leaf 9, the reduction of individual leaf size was the main factor responsible for the reduced LAI in the P0 treatment. After this stage, the delayed leaf appearance accounted for a great part of the reduced LAI in the P0 treatment.
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    Leaf endophyte Neotyphodium coenophialum modifies mineral uptake in tall fescue (2000)
    Springer
    Plant and soil 227 (2000), S. 115-126 
    Details
    ISSN: 1573-5036
    Keywords: endophyte ; mineral nutrition ; Neotyphodium coenophialum ; phosphorus ; tall fescue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Neotyphodium coenophialum (Morgan-Jones and Gams) Glenn, Bacon and Hanlin, a fungal endophyte found primarily in shoots of tall fescue (Festuca arundinacea Shreb.), can modify rhizosphere activity in response to phosphorus (P) deficiency. In a controlled environment experiment, two cloned tall fescue genotypes (DN2 and DN4) free (E-) and infected (E+) with their naturally occurring endophyte strains were grown in nutrient solutions at low P (3.1 ppm) or high P (31 ppm) concentrations for 21 d. Endophyte infection increased root dry matter (DM) of DN4 by 21% but did not affect root DM of DN2. Under P deficiency, shoot and total DM were not affected by endophyte but relative growth rate was greater in E+ than E- plants. In high P nutrient solution, E+ plants produced 13% less (DN2) or 29% more (DN4) shoot DM than E- plants. Endophyte affected mineral concentrations in roots more than in shoots. Regardless of P concentration in nutrient solution, E+ DN2 accumulated more P, Ca, Zn and Cu but less K in roots than E- plants. When grown in high P nutrient solution, concentrations of Fe and B in roots of E+ DN2 plants were reduced compared with those of E- plants. Concentrations of P, Ca and Cu in roots of DN4 were less, but K was greater in E+ than E- plants. In shoots, E+ DN2 had greater concentrations of Fe and Cu than E- DN2, regardless of P concentration in nutrient solution. Genotype DN4 responded to endophyte infection by reducing B concentration in shoots. Nutrient uptake rates were affected by endophyte infection in plants grown in low P nutrient solution. A greater uptake rate of most nutrients and their transport to shoots was observed in DN2, but responses of DN4 were not consistent. Results suggest that endophyte may elicit different modes of tall fescue adaptation to P deficiency.
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    The effects of slash burning on ecosystem nutrients during the land preparation phase of shifting cultivation (2000)
    Springer
    Plant and soil 220 (2000), S. 247-260 
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    ISSN: 1573-5036
    Keywords: cations ; fire ; nitrogen ; nutrients ; phosphorus ; slash-and-burn ; soil ; tropical forests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The most commonly observed change in soil following slash-and-burn clearing of tropical forest is a short-term increase in nutrient availability. Studies of shifting cultivation commonly cite the incorporation of nutrient-rich ash from consumed aboveground biomass into soil as the reason for this change. The effects of soil heating on nutrient availability have been examined only rarely in field studies of slash-and-burn, and soil heating as a mechanism of nutrient release is most often assumed to be of minor importance in the field. Few budgets for above and belowground nutrient flux have been developed in the tropics, and a survey of results from field and laboratory studies indicates that soils are sufficiently heated during most slash-and-burn events, particularly in dry and monsoonal climates, to cause significant, even substantial release of nutrients from non-plant-available into plant-available forms in soil. Conversely, large aboveground losses of nutrients during and after burning often result in low quantities of nutrients that are released to soil. Assessing the biophysical sustainability of an agricultural practice requires detailed information about nutrient flux and loss incurred during management. To this end, current conceptual models of shifting cultivation should be revised to more accurately describe these fluxes and losses.
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    The importance of root gravitropism for inter-root competition and phosphorus acquisition efficiency: results from a geometric simulation model (2000)
    Springer
    Plant and soil 218 (2000), S. 159-171 
    Details
    ISSN: 1573-5036
    Keywords: competition ; roots ; common bean ; mineral nutrition ; models ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We have observed that low soil phosphorus availability alters the gravitropic response of basal roots in common bean (Phaseolus vulgaris L.), resulting in a shallower root system. In this study we use a geometric model to test the hypotheses that a shallower root system is a positive adaptive response to low soil P availability by (1) concentrating root foraging in surface soil horizons, which generally have the highest P availability, and (2) reducing spatial competition for P among roots of the same plant. The growth of nine root systems contrasting in gravitropic response over 320 h was simulated in SimRoot, a dynamic three-dimensional geometric model of root growth and architecture. Phosphorus acquisition and inter-root competition were estimated with Depzone, a program that dynamically models nutrient diffusion to roots. Shallower root systems had greater P acquisition per unit carbon cost than deeper root systems, especially in older root systems. This was due to greater inter-root competition in deeper root systems, as measured by the volume of overlapping P depletion zones. Inter-root competition for P was a significant fraction of total soil P depletion, and increased with increasing values of the P diffusion coefficient (De), with root age, and with increasing root gravitropism. In heterogenous soil having greater P availability in surface horizons, shallower root systems had greater P acquisition than deeper root systems, because of less inter-root competition as well as increased root foraging in the topsoil. Root P acquisition predicted by SimRoot was validated against values for bean P uptake in the field, with an r 2 between observed and predicted values of 0.75. Our results support the hypothesis that altered gravitropic sensitivity in P-stressed roots, resulting in a shallower root system, is a positive adaptive response to low P availability by reducing inter-root competition within the same plant and by concentrating root activity in soil domains with the greatest P availability.
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    URL: http://dx.doi.org/10.1023/A:1014987710937
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    Uptake of P from apatite by Pinus sylvestris seedlings colonised by different ectomycorrhizal fungi (2000)
    Springer
    Plant and soil 218 (2000), S. 249-256 
    Details
    ISSN: 1573-5036
    Keywords: ectomycorrhiza ; phosphorus ; Paxillus ; Suillus ; weathering ; ergosterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The role of ectomycorrhizal (EM) fungi in increasing apatite dissolution was tested in a pot system with Pinus sylvestris (L.) seedlings growing in a sand/peat mixture. Non-mycorrhizal seedlings and seedlings inoculated with one of three different isolates of EM fungi were grown for 210 days in pots divided into a root-containing and a root-free compartment. The EM mycelium was allowed to colonise the root-free compartment, to which apatite had been added as a P source in half of the pots. All mineral nutrients except P were supplied in the form of a balanced nutrient solution. Seedlings grown with apatite as their P source grew significantly better and had higher P concentrations (1.1–1.5 mg/g) compared with seedlings growing without any P source (0.6–1.0 mg/g), indicating that they were able to use apatite-P. A weathering budget based on P uptake indicated that 6.7–18.9 mg apatite was weathered per pot which corresponds to 0.3–0.9% of the added apatite. A similar budget based on Sr uptake indicated that the apatite weathering rate was lower (0.13-0.3%). One Suillus variegatus isolate and an unidentified fungus had a significant positive influence on the dissolution of apatite, while another S. variegatus isolate had colonised roots poorly and did not influence weathering significantly. Oxalic acid was detected in root-free soil and was especially abundant in compartments colonised by S. variegatus. The concentration of oxalic acid was correlated to the concentration of phosphate in the soil solution of root-free soil, indicating that oxalic acid influences apatite dissolution.
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    URL: http://dx.doi.org/10.1023/A:1014936217105
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    On variation in forest floor thickness across four red pine plantations in Pennsylvania, USA (2000)
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    Plant and soil 219 (2000), S. 57-69 
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    ISSN: 1573-5036
    Keywords: decomposition ; litter quality ; mycorrhiza ; nitrogen ; phosphorus ; saprotrophic microorganisms ; tannins ; forest soils ; acidification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We studied variation in forest floor thickness in four plantations of red pine (Pinus resinosa Ait.) which were similar in age, soil type and associated vegetation. The plantations were located (west to east) in the Clear Creek, Moshannon, Sproul and Tiadaghton State Forests of Pennsylvania, USA. A gradient in forest floor thickness exists across these plantations; the forest floor is thickest in the west and it becomes progressively thinner toward the east. Decomposition of imported litter increased from west to east, suggesting that the variation in forest floor thickness is related to variation in the rate of decomposition. Decomposition rates were related to saprotroph abundance. Variation in forest floor N and phenolic concentrations, in overall mycorrhiza density and in the relative proportions of three common mycorrhiza morphotypes could not explain the variation in decomposition rate. The P concentrations and pH of the forest floor were significantly lower at Clear Creek and Moshannon, where decomposition rates were lowest, compared to Sproul and Tiadaghton, where decomposition rates were most rapid. This suggests that P concentration and pH may have exerted some control on decomposition.
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    Growth analysis of maize field crops under phosphorus deficiency. II. Radiation-use efficiency, biomass accumulation and yield components (2000)
    Springer
    Plant and soil 224 (2000), S. 259-272 
    Details
    ISSN: 1573-5036
    Keywords: light interception ; phosphorus ; radiation-use efficiency ; yield components ; Zea mays L.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Biomass accumulation by crops depends on both light interception by leaves and on the efficiency with which the intercepted light is used to produce dry matter. Our aim was to identify which of these processes were affected for maize (Zea mays L., cv Volga) field crops grown under phosphorus (P) deficiency. In the preceding paper (Plénet et al., 2000), it was shown that P deficiency severely reduced leaf growth. In this paper, the effect of P deficiency on the radiation-use efficiency (RUE) was investigated. The experimental work was carried out in 1995, 1996 and 1997 on a long-term P fertilisation trial located on a sandy soil in the south-west of France. Three P fertilisation regimes have been applied since 1972: no- P (P0 treatment) and different rates of P fertiliser (P1.5: 1.5 times the grain P export and P3: 3 times the grain P export). These fertilisation regimes have led to contrasted levels of soil P supply. Only slight differences were observed between the P1.5 and P3 treatment for above-ground biomass accumulation and grain yield. Conversely the grain yield was significantly reduced in P0 (−11%). Above-ground biomass production was severely reduced, with the maximum difference between treatment (−60% in P0) occurring between 400 and 600 °C days after sowing. The lower biomass production in P0 was accounted for by the reduced amount of photosynthetically active radiation (PAR) absorbed by the canopy, which was itself the consequence of the reduced leaf area index (see Plénet et al., 2000). The calculated RUE were found to depend on the plant stage, especially during the pre-flowering period, and on the average air temperature. No effect of P deficiency was observed on the calculated RUE, even during the period when above-ground biomass accumulation was the most severely reduced. These results obtained in field crop conditions strengthen the idea that P deficiency affects plant growth, especially leaf growth, earlier and to a greater extent than photosynthesis per unit leaf area.
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    URL: http://dx.doi.org/10.1023/A:1004835621371
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    Autumn leaf colours as indicators of decomposition rate in sycamore (Acer pseudoplatanus L.) (2000)
    Springer
    Plant and soil 225 (2000), S. 33-38 
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    ISSN: 1573-5036
    Keywords: deciduous tree ; foliar pigmentation ; fungus ; litter mass loss ; nitrogen ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We tested the hypothesis that there is a causal connection between autumn colour, nutrient concentration and decomposibility of fresh leaf litter. Samples from patches of different autumn colours within the leaves of the deciduous tree sycamore (Acer pseudoplatanus) were sealed into litter bags and incubated for one winter in an outdoor leaf mould bed. Green leaf patches were decomposed faster than yellow or brown patches and this corresponded with the higher N and P concentrations in the former. Black patches, indicating colonisation by the tar spot fungus Rhytisma acerinum, were particularly high in P, but were decomposed very slowly, owing probably to resource immobilisation by the fungus. The results supported the hypothesis and were consistent with a previous study reporting an interspecific link between autumn coloration and decomposition rate. Autumn leaf colour of deciduous woody plants may serve as a useful predictor of litter decomposibility in ecosystem or biome scale studies where extensive direct measurements of litter chemistry and decomposition are not feasible.
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    URL: http://dx.doi.org/10.1023/A:1026530214258
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    Phosphatase activity of extra-radical arbuscular mycorrhizal hyphae: A review (2000)
    Springer
    Plant and soil 226 (2000), S. 199-210 
    Details
    ISSN: 1573-5036
    Keywords: Histochemical staining ; mineral nutrition ; phosphorus ; stress ; vital staining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Phosphatase activity of arbuscular mycorrhizal (AM) fungi has attracted attention in three fairly distinct domains: intracellular enzymes with defined metabolic functions that have been studied in intraradical hyphae, histochemical staining of alkaline phosphatase as an indicator of fungal activity measured both intra- and extraradically, and extracellular activity related to mineralization of organic P (Po) compounds that may enhance mycorrhizal utilization of an important nutrient pool in soil. This review focuses on the latter subjects with emphasis on extraradical mycelium (ERM), while it draws on selected data from the vast material available concerning phosphatases of other organisms. We conclude that histochemical staining of alkaline phosphatase is a sensitive and suitable method for monitoring the effect of adverse conditions encountered by ERM both as a symbiotically functional entity in soil, and in vitro without modifying interference of soil or other solid substrates. Furthermore, the quantitative importance of extracellular enzymes for P nutrition of AM plants is estimated to be insignificant. This is concluded from the low quantitative contribution extracellular hyphae of AM fungi give to the total phosphatase activity in soil, and from estimations of which processes that may be rate limiting in organic P mineralization. Maximum values for the former is in the order of a few percent. As for the latter, solubilization of Po seems to be far more important than Po hydrolysis for utilization of Po by AM fungi and plants, as both endogenous soil phosphatase activity and phosphatases of other soil organisms are ubiquitous and abundant. Our discussion of mycorrhizal phosphatases supports the view that extracellular phosphatases of roots and micro-organisms are to a large extent released incidentally into soil, and that the source has limited benefit from its activity.
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    URL: http://dx.doi.org/10.1023/A:1026582207192
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    Response of tomato plants to chilling stress in association with nutrient or phosphorus starvation (2000)
    Springer
    Plant and soil 226 (2000), S. 99-106 
    Details
    ISSN: 1573-5036
    Keywords: chilling ; chlorophyll fluorescence ; nutrient ; phosphorus ; photosynthesis ; starvation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The experiments were conducted on two tomato cultivars: Garbo and Robin. Mineral starvation due to plant growth in 20-fold diluted nutrient solution (DNS) combined with chilling reduced the rate of photosynthesis (P N) and stomatal conductance (g) to a greater extent than in plants grown in full nutrient solution (FNS). In phosphate-starved tomato plants the P N rate and stomatal conductance decreased more after chilling than in plants grown on FNS. In low-P plants even 2 days after chilling the recovery of CO2 assimilation rate and stomatal conductance was low. A resupply of phosphorus to low-P plants (low P + P) did not improve the rate of photosynthesis in non-chilled plants (NCh) but prevented PN inhibition in chilled (Ch) plants. The greatest effect of P resupply was expressed as a better recovery of photosynthesis and stomatal conductance, especially in non-chilled low P + P plants. The F v/F m (ratio of variable to maximal chlorophyll fluorescence) decreased more during P starvation than as an effect of chilling. Supplying phosphorus to low-P plants caused the slight increase in the F v/F mratio. In conclusion, after a short-term chilling in darkness a much more drastic inhibition of photosynthesis was observed in nutrient-starved or P-insufficient tomato plants than in plants from FNS. This inhibition was caused by the decrease in both photochemical efficiency of photosystems and the reduction of stomatal conductance. The presented results support the hypothesis that tomato plants with limited supply of mineral nutrients or phosphorus are more susceptible to chilling.
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    A function of cyanobacterial mats in phosphorus-limited tropical wetlands (2000)
    Springer
    Hydrobiologia 431 (2000), S. 135-153 
    Details
    ISSN: 1573-5117
    Keywords: cyanobacteria ; wetlands ; biomass ; phosphorus ; nitrogen fixation ; alkaline phosphatase ; Belize
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Cyanobacterial mats are important components of oligotrophic wetland ecosystems in the limestone-based regions of the Caribbean. Our goals were to: (1) Estimate the biomass and primary production of cyanobacterial mats, quantify the extent of nitrogen fixation and measure the activity of alkaline phosphatase (APA) in representative marshes of northern Belize; (2) Record changes in these variables following nutrient additions. The mat biomass ranged from 200 to 700 g m−2 AFDM, with the epipelon contributing up to 87% of the total. Tissue nitrogen was similar in all marshes (1.1–1.5%), while tissue phosphorus was extremely low (0.0055–0.0129%) and well correlated with the N:P ratio in water. Nitrogen fixation expressed as nitrogenase activity was high in some marshes (17.5 nmol C2H4 cm−2 h−1) and low (〈 5 nmol C2H4 cm−2 h−1) in others depending mainly on the proportion of heterocyst-forming cyanobacteria (Nostocales, Stigonematales) in the mat. Alkaline phosphatase activity was positively correlated with the N:P ratio of the mat. Experimental addition of phosphorus resulted in significant increase in primary production and nitrogen fixation while it suppressed the APA activity. The presented data clearly showed that oligotrophic marshes of northern Belize are strongly P limited. Increased input of phosphorus would profoundly change their structure and functions.
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    Nitrogen limitation of production in a Californianannual grassland: The contribution of arbuscularmycorrhizae (2000)
    Springer
    Biogeochemistry 49 (2000), S. 37-51 
    Details
    ISSN: 1573-515X
    Keywords: Arbuscular mycorrhizae/Vesicular-arbuscular mycorrhizae (AM/VAM) ; annual grasslands ; benomyl ; nitrogen limitation ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Nutrient availability limits plant production acrossa wide range of terrestrial ecosystems. In this studyof a Californian annual grassland community, theinfluence of arbuscular mycorrhizal (AM) associationson plant nutrient acquisition was investigated usingfactorial combinations of nitrogen (N), phosphorus (P)and benomyl fungicide. N additions resulted in asignificant increase in shoot biomass demonstratingthat plant productivity in these soils was N-limited. The effect of P additions consistently depended onfungicide treatment. In the absence of benomyl, shootP accumulation was unaltered by P addition. In thepresence of benomyl, P addition significantlyincreased shoot P accumulation and was associated witha consistent trend towards enhanced shoot biomass.The induction of P-deficiency with benomylapplication suggests that effective P acquisition byAM may contribute to the strong N-limitation ofproduction observed in many terrestrial ecosystems.
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    Nutrient losses in runoff from grasslandand shrubland habitats in southern New Mexico: II. Field plots (2000)
    Springer
    Biogeochemistry 49 (2000), S. 69-86 
    Details
    ISSN: 1573-515X
    Keywords: Bouteloua eriopoda ; Chihuahuan Desert ; desertification ; hydrology ; Larrea tridentata ; nitrogen ; nutrient budgets ; phosphorus ; runoff
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Losses of dissolved nutrients (N, P, K, Ca, Mg, Na,Cl, and SO4) in runoff were measured on grasslandand shrubland plots in the Chihuahuan desert ofsouthern New Mexico. Runoff began at a lowerthreshold of rainfall in shrublands than ingrasslands, and the runoff coefficient averaged 18.6%in shrubland plots over a 7-year period. In contrast,grassland plots lost 5.0 to 6.3% of incidentprecipitation in runoff during a 5.5-year period. Nutrient losses from shrubland plots were greater thanfrom grassland plots, with nitrogen losses averaging0.33 kg ha−1 yr−1 vs0.15 kg ha−1 yr−1, respectively, during a 3-year period. Thegreater nutrient losses in shrublands were due tohigher runoff, rather than higher nutrientconcentrations in runoff. In spite of these nutrientlosses in runoff, all plots showed net accumulationsof most elements due to inputs from atmosphericdeposition. Therefore, loss of soil nutrients byhillslope runoff cannot, by itself, account for thedepletion of soil fertility associated withdesertification in the Chihuahuan desert.
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    2-Methylisoborneol disposition in three strains of catfish: absence of biotransformation (2000)
    Springer
    Fish physiology and biochemistry 23 (2000), S. 225-232 
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    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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    Sampling Strategies for Mapping Soil Phosphorus and Soil Potassium Distributions in Cool Temperate Grassland (2000)
    Springer
    Precision agriculture 2 (2000), S. 347-357 
    Details
    ISSN: 1573-1618
    Keywords: grassland soils ; mapping ; phosphorus ; potassium ; sampling strategies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Unlike the situation for arable soils, virtually nothing is known about the spatial dependencies of soil properties in cool temperate grassland or about what the optimal sampling strategies ought to be for mapping soil nutrient distributions in such situations. The aim of this study was to investigate the spatial variability in ‘plant-available’ (soil) phosphorus and potassium in a grass silage field in Northern Ireland and devise ‘optimal’ sampling strategies for mapping their distributions. Soil samples were collected from the field at 25 m intervals in a regular rectangular grid to provide a database of soil properties. Different data combinations were subsequently abstracted from this database for comparison purposes, and ordinary kriging used to produce interpolated soil maps. Soil potassium displayed greater spatial variability than soil phosphorus. In keeping with this observation, the results of three separate statistical procedures demonstrated that the optimal sample size for estimating the ‘true’ population means was about twice as large for soil potassium as for soil phosphorus. Optimal sampling strategies, however, related not just to sample size but to sample combination and field shape as well.
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    Phosphorus (P) management in the ‘De Marke’ dairy farming system (2000)
    Springer
    Nutrient cycling in agroecosystems 56 (2000), S. 219-229 
    Details
    ISSN: 1573-0867
    Keywords: phosphorus ; P ; dairy farming ; systems research ; environment ; pollution ; soil fertility ; sandy soils
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In the sandy regions of the Netherlands water quality is threatened by high losses of nutrients from intensive dairy farms. About 67% (32 kg ha-1yr-1) of farm inputs of P in purchased feeds and fertilisers do not leave in milk or cattle. The Dutch government defined decreasing maximum permitted nutrient surplusses for the period 1998–2008, at 9 kg ha-1yr-1 for P. Farmers suppose that reducing the surplusses will be costly, because it limits application of slurry, which then has to be either exported or additional land has to be purchased. Moreover, farmers are worried about the impact on soil fertility and crop growth. To explore the possibilities of reducing surplusses by improved management, farming systems research is carried out at prototype farm ‘De Marke’. Results indicate that average intensive dairy farms can reduce P surplus sufficiently, without the need to buy land or to export slurry. Key factors are reductions in purchased feeds (by reduced needs per kg milk as a result of a higher milk yield per cow, less young stock and judicious feeding) and fertilisers (by improved management of ‘home-made’ manure and an increased maize area). Initially, P fertility status of the fields of ‘De Marke’ decreased, but stabilised in the seventh year at a level not restrictive to crop production.
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    Tithonia diversifolia as a green manure for soil fertility improvement in western Kenya: A review (2000)
    Springer
    Agroforestry systems 49 (2000), S. 201-221 
    Details
    ISSN: 1572-9680
    Keywords: biomass transfer ; integrated nutrient management ; nitrogen ; nutrient cycling ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Tithonia diversifolia, a shrub in the family Asteraceae, is widely distributed along farm boundaries in the humid and subhumid tropics of Africa. Green biomass of tithonia has been recognized as an effective source of nutrients for lowland rice (Oryza sativa) in Asia and more recently for maize (Zea mays) and vegetables in eastern and southern Africa. This paper reviews the potential of tithonia green biomass for soil fertility improvement based on recent research in western Kenya. Green leaf biomass of tithonia is high in nutrients, averaging about 3.5% N, 0.37% P and 4.1% K on a dry matter basis. Boundary hedges of sole tithonia can produce about 1 kg biomass (tender stems + leaves) m−1 yr−1 on a dry weight basis. Tithonia biomass decomposes rapidly after application to soil, and incorporated biomass can be an effective source of N, P and K for crops. In some cases, maize yields were even higher with incorporation of tithonia biomass than with commercial mineral fertilizer at equivalent rates of N, P and K. In addition to providing nutrients, tithonia incorporated at 5 t dry matter ha−1 can reduce P sorption and increase soil microbial biomass. Because of high labor requirements for cutting and carrying the biomass to fields, the use of tithonia biomass as a nutrient source is more profitable with high-value crops such as vegetables than with relatively low-valued maize. The transfer of tithonia biomass to fields constitutes the redistribution of nutrients within the landscape rather than a net input of nutrients. External inputs of nutrients would eventually be required to sustain production of tithonia when biomass is continually cut and transferred to agricultural land.
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    URL: http://dx.doi.org/10.1023/A:1006339025728
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    Stock-type patterns of phosphorus uptake, retranslocation, net photosynthesis and morphological development in interior spruce seedlings (2000)
    Springer
    New forests 19 (2000), S. 27-49 
    Details
    ISSN: 1573-5095
    Keywords: Picea glauca (Moench) Voss × Picea engelmannii Parry ; phosphorus ; phosphorus-use efficiency ; retranslocation ; specific absorption rate ; spring-stock ; stock-type ; summer-stock
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract One-year-old interior spruce (Picea glauca (Moench) Voss × Picea engelmannii Parry) spring-stock and summer-stock were grown under two phosphorus (P) fertility regimes, with (+P) or without (−P), followed by a simulated winter, and a second growing period under an adequate fertility regime in a controlled environment room. The two stock-types differed in their response to low P availability. For spring-stock, morphological development, phosphorus-use efficiency (PUE) and P specific absorption rate (SAR) were similar between −P and +P seedlings. For summer-stock, −P seedlings compared to +P seedlings had lower (p ≤ 0.05) morphological development, but greater PUE and SAR. For both stock-types, P content increased in +P seedlings, remained low in −P seedlings, and P concentration decreased in nursery-needles (i.e., formed in the nursery) of −P seedlings. The difference in stock-type response to low phosphorus availability (−P) was attributed to internal supply of P and it's retranslocation. Assimilation (A) of CO2 in nursery-needles was similar between −P and +P seedlings for both stock-types. For spring-stock, +P seedlings had greater A in new-needles (i.e., needles formed during the trial) than −P seedlings. It was recommended that the spring-stock be selected over summer-stock for sites low in P availability.
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    URL: http://dx.doi.org/10.1023/A:1006618312161
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    Traits associated with improved P-uptake efficiency in CIMMYT's semidwarf spring bread wheat grown on an acid Andisol in Mexico (2000)
    Springer
    Plant and soil 221 (2000), S. 189-204 
    Details
    ISSN: 1573-5036
    Keywords: Andisol ; phosphatases ; phosphorus ; roots ; VA mycorrhiza ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Phosphorus deficiency is a major yield limiting constraint in wheat cultivation on acid soils. The plant factors that influence P uptake efficiency (PUPE) are mainly associated with root characteristics. This study was conducted to analyze the genotypic differences and relationships between PUPE, root length density (RLD), colonization by vesicular arbuscular and arbuscular mycorrhizal (V)AM fungi and root excretion of phosphatases in a P-deficient Andisol in the Central Mexican Highlands. Forty-two semidwarf spring-bread-wheat (Triticum aestivumL.) genotypes from CIMMYT were grown without (−P) and with P fertilization (+P), and subsequently in subsets of 30 and 22 genotypes in replicated field trials over 2 and 3 years, respectively. Acid phosphatase activity at the root surface (APASE) was analyzed in accompanying greenhouse experiments in nutrient solution. In this environment, PUPE contributed more than P utilization efficiency, in one experiment almost completely, to the variation of grain yield among genotypes. Late-flowering genotypes were higher yielding, because the postanthesis period of wheat was extended due to the cold weather at the end of the crop cycles, and postanthesis P uptake accounted for 40–45% of total P uptake. PUPE was positively correlated with the numbers of days to anthesis (at −P r=0.57 and at +P r=0.73). The RLD in the upper soil layer (0–20 cm) of the wheat germplasm tested ranged from 0.5 to 2.4 cm cm-3 at –P and 0.7 to 7.7 at +P. RLD was the most important root trait for improved P absorption, and it was positively genetically correlated with PUPE (at –P r=0.42 and at +P r=0.63) and the number of spikes m-2 (at –P r=0.58 and at +P r=0.36). RLD in the upper soil layer was more important with P fertilizer application. Without P fertilization, root proliferation in the deeper soil profile secured access to residual, native P in the deeper soil layer. (V)AM-colonisation and APASE were to a lesser degree correlated with PUPE. Among genoptypes, the level of (V)AM-colonisation ranged from 14 to 32% of the RLD in the upper soil layer, and APASE from 0.5 to 1.1 nmol s-1 plant-1 10-2.
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    Temporal changes in C, P and N concentrations in soil solution following application of synthetic sheep urine to a soil under grass (2000)
    Springer
    Plant and soil 222 (2000), S. 1-13 
    Details
    ISSN: 1573-5036
    Keywords: carbon ; defoliation ; nitrogen ; phosphorus ; sheep urine ; soil solution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We have determined the temporal changes in the concentration of dissolved organic carbon (DOC) and P and N components in soil solution following application of synthetic sheep urine (500 kg N ha-1) to a brown forest soil in boxes sown with Agrostis capillaris. Three contrasting defoliation treatments (no cutting, single cut before urine application and regular cutting twice per week) plus a fallow soil were studied. The synthetic urine contained 15N labelled urea and was P-free. Intact soil cores were taken after 2, 7, 14, 21 and 56 d and centrifuged to obtain soil solution. The urea in the synthetic urine was rapidly hydrolysed in the soil, increasing soil solution pH, DOC and total dissolved phosphorus (TDP) concentrations. For the regularly defoliated sward, DOC and P reached maximum concentrations (4000 mg DOC L-1 and 59 mg TDP L-1) on day 7. From their peak values, pH and DOC and P concentrations generally decreased with time and at day 56 were near those of the control. Concentrations of NH4 + and NO3 - in the no-urine treatments fluctuated and the greatest treatment differences were between the fallow soil and the soil sown with grass. Adding synthetic urine increased NH4 + concentrations during the first week, but NO3 - concentrations decreased. This was consistent with the 15N labelling of the NO3 - pool which required 3 weeks to reach that of 15NH4 +. Dissolved organic nitrogen (DON) reached a maximum value at day 7 with a concentration of 409 mg N L-1. The DON in soil solution contained no detectable amounts of 15N label indicating that it was derived from sources in the soil. Differences in soil solution composition related to the effect of the other cutting treatments and the fallow treatment were small compared to the effect of synthetic urine addition.
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    URL: http://dx.doi.org/10.1023/A:1004799323646
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    Root-induced increases in soil pH and nutrient availability to field-grown cereals and legumes on acid sandy soils of Sudano-Sahelian West Africa (2000)
    Springer
    Plant and soil 225 (2000), S. 117-127 
    Details
    ISSN: 1573-5036
    Keywords: anion/cation uptake ; cowpea ; millet ; phosphorus ; rhizosphere
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A field experiment with millet (Pennisetum glaucum L.), sorghum [Sorghum bicolor (L.) Moench], cowpea (Vigna unguiculata L.) and groundnut (Arachnis hypogeae L.) was conducted on severely P-deficient acid sandy soils of Niger, Mali and Burkina Faso to measure changes in pH and nutrient availability as affected by distance from the root surface and by mineral fertiliser application. Treatments included three rates of phosphorus (P) and four levels of nitrogen (N) application. Bulk, rhizosphere and rhizoplane soils were sampled at 35, 45 and 75 DAS in 1997 and at 55 and 65 DAS in 1998. Regardless of the cropping system and level of mineral fertiliser applied, soil pH consistently increased between 0.7 and two units from the bulk soil to the rhizoplane of millet. Similar pH gradients were observed in cowpea, but pH changes were much smaller in sorghum with a difference of only 0.3 units. Shifts in pH led to large increases in nutrient availability close to the roots. Compared with the bulk soil, available P in the rhizoplane was between 190 and 270% higher for P-Bray and between 360 and 600% higher for P-water. Exchangeable calcium (Ca) and magnesium (Mg) levels were also higher in the millet rhizoplane than in the bulk soil, whereas exchangeable aluminium (Al) levels decreased with increasing pH close to the root surface. The results suggest an important role of root-induced pH increases for crops to cope with acidity-induced nutrient deficiency and Al stress of soils in the Sudano-Sahelian zone of West Africa.
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    URL: http://dx.doi.org/10.1023/A:1026570406777
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    Nutrient enrichment of northern rivers in response to pulp mill and municipal discharges (2000)
    Springer
    Journal of aquatic ecosystem stress and recovery 8 (2000), S. 53-66 
    Details
    ISSN: 1573-5141
    Keywords: Canada ; nitrogen ; periphyton ; phosphorus ; pulp mill effluent ; rivers ; sewage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To evaluate the effects of pulp mill and municipal sewageeffluents on the nitrogen (N) and phosphorus (P) status of northernCanadian rivers, the Northern River Basins Study required an integratedresearch and assessment program consisting of field observation andexperimentation. Analysis of monitoring data collected over 3–13 yshowed that on an annual basis, pulp mills contributed 22% of theP and 20% of the N load discharged from the Wapiti to the Smokyriver, and 6 to 16% of the P load and 4 to 10% of the Nload in the Athabasca River. Despite these low contributions, N and Pconcentrations were elevated below pulp mill discharges on all threerivers during the low discharge period of September to April. Insitu experiments conducted with nutrient diffusing substrata showedthat periphyton biomass was maintained at low levels by insufficient Pin the upper reaches of the Athabasca River and insufficient N+P inthe Wapiti River upstream of point-source discharges. In contrast,effluent loading from pulp mill and sewage inputs alleviated nutrientlimitation downstream of major discharges on both rivers. Experimentsconducted in artificial streams located beside the Athabasca Riverupstream of the first pulp mill showed that P addition increasedperiphyton biomass (expressed as chlorophyll a content) suchthat biomass increased sharply at low P concentrations (2–5µg/L soluble reactive P) and approached saturation at 35µg/L soluble reactive P. As a result of recommendations fromthis integrated program of river monitoring and experimentation,nutrient loading has been reduced to the most affected river(Wapiti-Smoky) and federal and provincial departments of environment arereviewing loading limits for other river reaches.
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    URL: http://dx.doi.org/10.1023/A:1011447907574
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    Light- and nutrient-limited periphyton in low order streams of Oahu, Hawaii (2000)
    Springer
    Hydrobiologia 432 (2000), S. 101-111 
    Details
    ISSN: 1573-5117
    Keywords: Hawaii ; light ; nitrogen ; nutrients ; periphyton ; phosphorus ; spate ; stream
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To date, most studies of light- and nutrient-limited primary productivity in forested streams have been carried out in deciduous forests of temperate, continental regions. Conceptual models of light and nutrient limitation have been developed from these studies, but their restricted geographic range reduces the generality of such models. Unlike temperate continental streams, streams on tropical high islands are characterized by flashy, unpredictable discharge and riparian canopies that do not vary seasonally. These contrasting conditions suggest that patterns of light and nutrient limitation in tropical streams may differ from those in temperate streams. The effects of light, and nitrogen and phosphorus availability on periphyton accrual (measured as chlorophyll a per unit area) were investigated using field experiments in 4 low-order streams on the island of Oahu, Hawaii. Levels of chlorophyll a in partially-shaded stream pools were significantly greater than in heavily-shaded pools, and nutrient-enrichment increased the level of chlorophyll a in partially-shaded pools but not in heavily-shaded pools. In each stream, phosphate enrichment resulted in an increase in the level of chlorophyll a, but nitrate enrichment had no effect. Spates following rainstorms occur frequently in these streams, and may increase periphyton productivity by increasing the flux of nutrients to algal cells. However, differences in inorganic nitrogen and phosphorus concentrations measured during spates and baseflow were small, and during some spates, concentrations of these two nutrients declined relative to baseflow concentrations. These observations suggest that phosphorus limitation was not alleviated by spates.
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    URL: http://dx.doi.org/10.1023/A:1004074004416
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    Effects of the emergent macrophyte Juncus effusus L. on the chemical composition of interstitial water and bacterial productivity (2000)
    Springer
    Biogeochemistry 48 (2000), S. 307-322 
    Details
    ISSN: 1573-515X
    Keywords: aquatic plants ; dissolved organic carbon ; nutrient cycling ; phosphorus ; sediments ; wetlands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Release of oxygen from the roots ofaquatic macrophytes into anaerobic sediments canaffect the quantity of interstitial dissolved organicmatter and nutrients that are available to bacteria. Nutrient and dissolved organic carbon (DOC)concentrations were compared between subsurface(interstitial) waters of unvegetated sediments andsediments among stands of the emergent herbaceousmacrophyte Juncus effusus L. in a lotic wetlandecosystem. Concentrations of inorganic nitrogen(NH4 +, NO3 -, and NO2 -)were greater from sediments of the unvegetatedcompared to the vegetated zone. DOC concentrations ofinterstitial waters were greater in sediments of theunvegetated zone both in the winter and springcompared to those from the vegetated zone. AlthoughDOC concentrations in hydrosoils collected from bothzones increased from winter to spring, bacterialproductivity per mg DOC in spring decreased comparedto winter. Greater initial bacterial productivityoccurred on DOM collected from the vegetated comparedto the unvegetated zone in winter samples (days 1 and4), with increased bacterial productivity on samplescollected from the unvegetated zone at the end of thestudy (day 20). Bacterial productivity wassignificantly greater on all sampling days on DOM fromvegetated samples compared to unvegetated samples. In nutrient enrichment experiments, bacterialproductivity was significantly increased (p 〈 0.05)with phosphorus but not nitrogen only amendments.
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    Carbon, nitrogen and phosphorus cycling in rivermarginal wetlands; a model examination of landscapegeochemical flows (2000)
    Springer
    Biogeochemistry 50 (2000), S. 45-71 
    Details
    ISSN: 1573-515X
    Keywords: carbon ; landscape geochemical flows ; model ; nitrogen ; phosphorus ; wetland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract The importance of landscape geochemical flows wasinvestigated using a dynamic model simulating carbon,nitrogen and phosphorus cycling in riverine wetlands,which has been described in a previous paper. Thehydro-geomorphic unit (HGMU) concept was incorporatedin the model by defining a separate, completeunit-model for each unit (HGMU) within the wetland.These unit-models were connected by defining the flowsof nitrogen and phosphorus between them. These flows,also called landscape geochemical flows, usuallyconsist of flows of water containing N and P. The model was applied to a site at Kismeldon Meadows,in south-western England. This site consists of twounits, a slope and a floodplain, separated by a ditch,which catches most of the run off and shallowgroundwater flows from the slope. Only an estimated1% of the N and P that leaves the slope unit in thewater outflow reaches the floodplain unit; the rest iscaught in the system of ditches, which prevent thegeochemical flows taking their natural course. Toexamine the influence of this system of ditches, themodel was run for the same site, but without theditches. This is comparable to a situation of arestored site, where run off and shallow groundwaterflows containing nutrients, can freely get from theslope to the floodplain. The computer simulation experiment reconnecting theslope and floodplain showed that this (1) increasedthe nutrient input into the floodplain, causing ahigher biomass production, and (2) increased thewetness of the floodplain, causing slowerdecomposition, which together (3) led to a faster soilorganic matter accumulation in the floodplain.Nutrient inflows became relatively more importantcompared to atmospheric deposition, especially forphosphorus. By connecting the slope and the floodplainmore nitrogen and less phosphorus flowed into theriver.
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    Internal eutrophication in peat soils through competition between chloride and sulphate with phosphate for binding sites (2000)
    Springer
    Biogeochemistry 50 (2000), S. 183-194 
    Details
    ISSN: 1573-515X
    Keywords: chloride ; internal eutrophication ; nitrogen ; peat soil ; phosphorus ; phytometer ; sulphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Inputs of surface waters high in chloride and sulphateincreased the availability of nutrients in fenpeatlands. This `internal eutrophication' wasdemonstrated with test plants (`phytometers') andthrough water and soil analysis. Three experiments arepresented in which the level of chloride and/orsulphate was increased to 3 mmolc l−1. Inexperiment 1 chloride levels were increased from 0.5to 3 mmolc l−1 as CaCl2 or NaCl. Inexperiment 2 and 3 similar increased levels forchloride and sulphate (3 mmolc l−1; as NaCland Na2SO4) were used. The following resultswere found: (i) No differences in soil total-N and total-P werefound before and after the treatments in any of thethree experiments. (ii) Experiment 1 showed a significant increase inBio-Available P (BAP) in pots planted with Anthoxanthum odoratum as well as in bare pots for theNaCl and CaCl2 treatments. The plants in thesetreatments had taken up much more P. (iii) Experiment 2 showed an increase in soil BAPafter treatment with chloride and sulphate in potsplanted with Anthoxanthum odoratum. The chloridetreatment had no effect on plant biomass, whereas thesulphate treatment resulted in a reduction in rootbiomass and root N and P content. The shoots showedan increase in P content in the sulphate and chloridetreatments, while N content remained the same. (iv) In experiment 3, treatments with chloride andsulphate led to significantly increased biomass and Puptake of Anthoxanthum odoratum. Again, noeffects on N uptake were found. These experiments provide evidence for distinctlyincreased availability of phosphate in peat soils whenthese come into contact with water with evenmoderately increased sulphate or chloride levels.Surface water originating from the Rhine river, whichis enriched in chloride and sulphate, is oftensupplied to fen reserves in The Netherlands, tocompensate for water losses due to agriculturaldrainage in the region. The results of this study showthat phosphate availability to the vegetation may risedrastically, with detrimental effects on the speciesdensity and the occurrence of rare species in thevegetation. Hence, supply of this water should beavoided.
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    Al and Fe Biogeochemistry in a floodplain forest: Implications for P retention (2000)
    Springer
    Biogeochemistry 51 (2000), S. 1-32 
    Details
    ISSN: 1573-515X
    Keywords: aluminum ; floodplain forests ; iron ; organic matter ; P sorption capacity ; phosphorus ; soil ; wetlands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract We examined spatial and temporal variationsin soil chemistry in a floodplain forest landscape todetermine the effects of flooding on aluminum (Al) andiron (Fe) oxide biogeochemistry and inorganicphosphorus (Pi) sorption capacity. Whenpreviously sorbed Pi was considered, the sorptioncapacities of floodplain and adjacent upland soilswere comparable, suggesting that floodplain soilsrepresent a second line of defense protectingdownstream aquatic ecosystems from agriculturalrun-off. Pi sorption capacity was highlycorrelated with oxalate-extractable Al (Alo)(rs = 0.78); Alo and percent organic matter(OM) were also highly correlated (rs = 0.72),suggesting the importance of OM-Al complexes in thesesoils. The correlation of oxalate-extractable Fe(Feo) with OM (rs = 0.64) was improved(rs = 0.80) by removing lower elevation (swale)soils, suggesting that flooding inhibits theassociation of Feo with OM. Fe oxidecrystallinity decreased during seasonal flooding, buttotal extractable Fe did not change significantly. Fesolubilized during flooding was either replaced bysediment deposition (252 ± 3 mmol kg−1yr−1), and/or reprecipitated locally. Al oxidecrystallinity also decreased during flooding due to asignificant decline in NaOH-extractable Al (AlN). AlN concentrations subsequently returned topre-flooding levels, but sediment Al inputs (57 ±3 mmol kg−1 yr−1), were insufficient to account for this recovery. Observed Fetransformations suggest the importance offlooding-induced declines in soil redox potential toFe biogeochemistry; observed Al transformationssuggest the importance of complexation reactions withsoil OM to Al biogeochemistry in this floodplainforest.
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    Using Bacterial Growth on Insects to Assess Nutrient Impacts in Streams (2000)
    Springer
    Environmental monitoring and assessment 63 (2000), S. 431-446 
    Details
    ISSN: 1573-2959
    Keywords: aquatic bacteria ; benthic macroinvertebrates ; bioindicator ; eutrophication ; nitrogen ; phosphorus ; stream pollution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract A combination field and laboratorystudy was conducted to evaluate the ability of arecently developed bioindicator to detect detrimentalnutrient conditions in streams. The method utilizesbacterial growth on aquatic insects to determinenutrient impacts. Field investigations indicated thatelevated concentrations of nitrate and phosphate wereassociated with growth of filamentous bacteria oninsect body surfaces, and that there was a significantreduction in the density of major insect taxa in thenutrient-enriched stream reaches. Laboratoryinvestigations confirmed a strong linkage betweenbacterial growth and reduced survival of insects. Survival was examined for insects with bacterialinfestation ranging from 0% to greater than 50%coverage of the body surface. A threshold forcatastrophic mortality occurred at about 25% bodycoverage; there were few survivors above that amount. Based on these findings, the diagnostic endpoint forthe bioindicator is 25% body coverage by bacterialgrowth, a level that signifies major impacts and isalso easy to detect visually. This study providesadditional evidence that the insect-bacteriabioindicator is a reliable tool for assessing nutrientimpacts on stream macroinvertebrate communities. Thebioindicator should prove useful for identifyingnutrient-impacted sites as well as monitoring thesuccess of management actions to improve water quality.
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    c-Fos Expression by Dopaminergic Receptor Activation in Rat Hippocampal Neurons (2000)
    Springer
    Molecules and cells 10 (2000), S. 546-551 
    Details
    ISSN: 0219-1032
    Keywords: c-Fos ; Dopamine ; D1 ; Hippocampus ; Rat ; Synaptic Plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract While dopamine is likely to modulate hippocampal synaptic plasticity, there has been little information about how dopamine affects synaptic transmission in the hippocampus. The expression of IEGs including c-fos has been associated with late phase LTP in the CA1 region of the hippocampus. The induction of c-fos by dopaminergic receptor activation in the rat hippocampus was investigated by using semiquantitative RT-PCR and immuno-cytochemistry. The hippocampal slices which were not treated with dopamine showed little expression of c-fos mRNA. However, the induction of c-fos mRNA was detected as early as 5 min after dopamine treatment, peaked at 60 min, and remained elevated 5 h after treatment. Temporal profiles of increases in c-fos mRNA by R(+)-SKF-38393 (50 μM) and forskolin (50 μM) were similar to that of dopamine. An increase in [cAMP] was observed in dopamine-, SKF-, or forskolin-treated hippocampal slices. By immunocytochemical studies, control hippocampal cells showed little expression of c-Fos immunoreactivity. However, when cells were treated with dopamine, an increase in the expression of c-Fos immunoreactivity was observed after treatment for 2 h. The treatment of hippocampal neurons with R(+)-SKF38393 (50 μM) or forskolin (50 μM) also induced a significant increase in c-Fos expression. These results indicate that the dopamine D1 receptor-mediated cAMP dependant pathway is associated with the expression of c-Fos in the hippocampal neurons. These data are consistent with the possible role of endogenous dopamine on synaptic plasticity via the regulation of gene expression. Furthermore, these results imply that dopamine might control the process of memory storage in the hippocampus through gene expression.
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    URL: http://dx.doi.org/10.1007/s10059-000-0546-y
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    Absorption and Disposition of a Selective Aldosterone Receptor Antagonist, Eplerenone, in the Dog (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1426-1431 
    Details
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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    URL: http://dx.doi.org/10.1023/A:1007597713530
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    Safety, Toxicokinetics and Tissue Distribution of Long-Term Intravenous Liposomal Amphotericin B (ambisome®): A 91-day Study in Rats (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1494-1502 
    Details
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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    URL: http://dx.doi.org/10.1023/A:1007605024942
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    Biodistribution of Amphotericin B When Delivered Through Cholesterol Hemisuccinate Vesicles in Normal and A. Fumigatus Infected Mice (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1236-1242 
    Details
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
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    URL: http://dx.doi.org/10.1023/A:1026418814417
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    Evaluation of Using Dog as an Animal Model to Study the Fraction of Oral Dose Absorbed of 43 Drugs in Humans (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 135-140 
    Details
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
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    URL: http://dx.doi.org/10.1023/A:1007552927404
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    Mechanism-Based Modeling of Functional Adaptation Upon Chronic Treatment with Midazolam (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 321-327 
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    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
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    URL: http://dx.doi.org/10.1023/A:1007505223519
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    Nitrogen and Phosphorus Levels in Sediments from Tropical Catatumbo River (Venezuela) (2000)
    Springer
    Water, air & soil pollution 117 (2000), S. 27-37 
    Details
    ISSN: 1573-2932
    Keywords: eutrophication ; nitrogen ; phosphorus ; river ; sediment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Nitrogen (N) and phosphorus (P) concentrations were determined in sediment samples along the bed of Catatumbo river in both Colombian and Venezuelan territories until the river outlet in Maracaibo lake. Total phosphorus was determined by digestion with HCl followed by analysis using the ascorbic acid method and total nitrogen was done using the standard microkjeldahl method plus nitrate-nitrite. Ammonium, orthophosphate and nitrate were determined using standard methods after extraction steps. The mean concentrations along the river bed were found in an interval of 0.035 and 1.492 mg g-1 dry sed. for nitrogen and 0.027 and 1.039 mg g-1 dry sed. for phosphorus at 95% confidence level. The mean molar ratio N/P in the river bed was 4.42 and 3.46 for river outlet zones in the lake, which indicates that nitrogen is the limiting nutrient. For comparison with previous results of lake sediments from sites near the river outlet it was concluded that Catatumbo river is a significant source of nutrients to the Maracaibo Lake system because sediment nutrients concentrations from Catatumbo river were higher than the ones in Maracaibo Lake. Statistic studies showed significant differences between countries, zones and similar behaviour in the river bed as related to the affluent rivers.
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    External Phosphorus Load Estimates and P-Budget for the Hydroelectric Reservoir of Bort-les-Orgues, France (2000)
    Springer
    Water, air & soil pollution 119 (2000), S. 91-103 
    Details
    ISSN: 1573-2932
    Keywords: eutrophication ; external load ; mass balance ; P-export coefficient ; phosphorus ; reservoir
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper presents two methods used to estimate the externalphosphorus load for the hydroelectric reservoir ofBort-Les-Orgues (in France's `Massif Central' region). The Pload calculated from export coefficients (150 t yr-1) agreedwith field measurements taken during a one-year survey carriedout from March 1996 to February 1997 (121 t yr-1). Exportcoefficients represent a good option for estimating phosphorusloads of other reservoirs in the region of Bort-Les-Orgues,provided that they display similar characteristics. Theseexternal load estimates are greater than the maximum permissibleload for a mesotrophic lake calculated from the OECD equations(40 t yr-1); thus, a yearly reduction of about 60 t shouldideally be achieved. This target, however, is probably tooambitious, and measures to reduce both point and non-pointsources must be implemented for the reservoir to tbe mesotrophic.Moreover, Bort-Les-Orgues is a tourist area. As such, thepresence of algal blooms (a regular occurrence on the lake) dueto an excess of P in the lake's water inflow could actuallyexert a negative impact on regional economy.
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    Distributions of Mercury and Phosphorous in Everglades Soils From Water Conservation Area 3A, Florida, U.S.A. (2000)
    Springer
    Water, air & soil pollution 121 (2000), S. 133-159 
    Details
    ISSN: 1573-2932
    Keywords: Everglades ; mercury ; mobility ; peat ; phosphorus ; soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Soils in the southern half of Water Conservation Area3A are mostly peats with some organic-rich marls. Mercury contents of 64 surface samples over a500 km2 area average 28.7 ng cc-1 (209 ppb drysediment), which is typical of organic-rich soils. High Hg contents in Everglades fish are therefore notcaused by anomalously high soil Hg. Hg contents showno systematic lateral variation, consistent withdeposition from well-mixed atmospheric sources ratherthan nearby point sources or runoff from canals.Cores from 9 sites contain more Hg and P at or nearthe surface than at 20–30 cm depth. Hg and P contentsof individual cores correlate well and define separatebackground and anomalous populations. The subsurfacedistribution of P is determined largely by uptake bysawgrass and other plants. The correlation between Pand Hg suggests that, although atmospheric Hgdeposition has undoubtedly increased in recentdecades, postdepositional mobilization of Hg may beimportant in Everglades soils. This finding, togetherwith recent direct measurements of atmospheric Hgdeposition, indicates that previous estimates of Hgdeposition rates based on Everglades peat cores, whichassumed that Hg is immobile in peat after deposition,have yielded large overestimates.
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    URL: http://dx.doi.org/10.1023/A:1005214908516
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    Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration (2000)
    Springer
    Bulletin of experimental biology and medicine 129 (2000), S. 359-361 
    Details
    ISSN: 1573-8221
    Keywords: acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.
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    URL: http://dx.doi.org/10.1007/BF02439270
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    The Role of Plant Size and Nutrient Concentrations in Associations between Medicago, and Rhizobium and/or Glomus (2000)
    Springer
    Biologia plantarum 43 (2000), S. 221-226 
    Details
    ISSN: 1573-8264
    Keywords: alfalfa ; arbuscular mycorrhizal fungi ; nitrogen ; nitrogen-fixing bacteria ; phosphorus ; plant growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The aim of this research was to carry out a critical study of the method of obtaining size equivalence between non-symbiotic alfalfa and alfalfa associated with Glomus and/or Rhizobium by applying fixed addition rates of nutrients to the non-symbiotic controls. The experimental design included three nutrient response curves in which the levels of added phosphorus and/or nitrogen were constant during the whole plant growth process: 1) a phosphorus response curve, in order to compare the growth of double symbiotic plants with that of only-Rhizobium inoculated ones; 2) a nitrogen response curve, that consisted of a comparison between the growth of double symbiotic alfalfa and four treatments associated only with Glomus; 3) a phosphorus and nitrogen response curve, to compare the growth of non-inoculated alfalfa with that of double symbiotic plants. Although similar size was achieved among some treatments at harvest, shoot growth over time and nutrient concentrations in tissues differed, indicating that growth equivalence did not mean functional equivalence. A second experimental design was performed taking into account the establishment of microsymbionts for determining the adequate moment to add supplemental phosphorus and/or nitrogen. It included four treatments: a) double symbiotic plants (MR); b) plants inoculated with Rhizobium only (R); c) plants inoculated with Glomus only (M), and d) non-inoculated plants (N). Great similarity in terms of plant growth and nutrient contents in tissues were obtained. Moreover, symbiotic plants were able to produce similar dry matter than non-symbiotic ones under P and N limitations.
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    Detection and analysis of gastrointestinal sounds in normal and small bowel obstructed rats (2000)
    Springer
    Medical & biological engineering & computing 38 (2000), S. 42-48 
    Details
    ISSN: 1741-0444
    Keywords: Bowel sounds ; Rat ; Motility ; Body acoustics ; Signal detection ; Signal characterisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This study is aimed at detecting gastrointestinal sounds (GIS) and correlating their characteristics with gastrointestinal (GI) conditions. The central hypotheses are that GIS generation depends on the motility patterns and the mechanical properties of the gut, and that changes in those result in measurable differences in GIS. An animal model which included both healthy rats and those with small bowel obstruction (SBO) was developed. The acoustic bursts, of GIS were detected by amplitude thresholding the signal envelope. Three methods of envelope estimation were proposed and evaluated. Envelope estimation using a Hilbert transform was found to produce the best results in the current application. The duration and dominant frequency of each detected GIS event was estimated and clear differences between healthy and diseased rats were discovered. In the control state, GIS events were found to consistently be of relatively short duration (3–65ms). Although the majority of events in the SBO state had similar short duration, infrequent longer events were also detected and appeared to be pathognomonic. Long duration events (〉100 ms) occurred in each of seven obstructed, but in none of 14 non-obstructed, cases (p〈0.001). It is concluded that GIS analysis may prove useful in the non-invasive, rapid, and accurate diagnosis of SBO.
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    Methods and Applications of Inversion (2000)
    Springer
    In:  Berlin, 306 pp., Springer, vol. 2, no. XVI:, pp. 1-14, (ISBN: 0-387-30752-4)
    Details
    Publication Date: 2000
    Keywords: Textbook of geophysics ; Textbook of geology ; Textbook of mathematics ; Data analysis / ~ processing ; Modelling ; Inversion
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    Geomatic Methods for the Analysis of Data in the Earth Sciences (2000)
    Springer
    In:  New York, Springer, vol. 31, no. 3, pp. 2-203, (ISBN 0-87590-533-1)
    Details
    Publication Date: 2000
    Keywords: Data analysis / ~ processing ; Error analysis ; Handbook of geophysics ; Handbook of geodesy ; toolbox ; Statistical investigations ; Inversion ; Non-linear effects ; aerial ; images ; Diffraction ; Tomography ; 1214 ; Geodesy ; and ; gravity ; Geopotential ; theory ; and ; determination ; 1224 ; Photogrammetry ; remote ; sensing ; 0902 ; Exploration ; geophysics ; Computational ; methods, ; seismic ; Gruen ; Grun
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    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
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    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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    Is the inversion effect in rhesus monkeys face-specific? (1999)
    Springer
    Animal cognition 2 (1999), S. 123-129 
    Details
    ISSN: 1435-9456
    Keywords: Key words Face recognition ; Inversion ; Expertise ¶effect ; Matching-to-sample ;  Macaca mulatta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract This study investigated the face inversion effect in rhesus monkeys (Macaca mulatta). Face stimuli consisted of ten black-and-white examples of unfamiliar rhesus monkey faces, brown capuchin faces, and human faces. Two non-face categories included ten examples of automobiles and abstract shapes. All stimuli were presented in a sequential matching-to-sample format using an automated joystick-testing paradigm. Subjects performed significantly better on upright than on inverted presentations of automobiles, rhesus monkey and capuchin faces, but not human faces or abstract shapes. These results are inconsistent with data from humans and chimpanzees that show the inversion effect only for categories of stimuli for which subjects have developed expertise. The inversion effect in rhesus monkeys does not appear to be face-specific, and should therefore not be used as a marker of specialized face processing in this species.
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    Ni–Zn–P alloy deposition from sulfate bath: inhibitory effect of zinc (1999)
    Springer
    Journal of applied electrochemistry 29 (1999), S. 1171-1176 
    Details
    ISSN: 1572-8838
    Keywords: alloys ; cyclic voltammetry ; electrodeposition ; electroless deposition ; nickel ; phosphorus ; zinc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Electroless Ni–Zn–P alloy deposition from a sulphate bath, containing sodium hypophosphite as reducer, was investigated. To increase the plating rate, the deposition parameters were optimized. The effect of process parameters (T, pH and [Zn2+]) on the plating rate and deposit composition was examined and it was found that the presence of zinc in the bath has an inhibitory effect on the alloy deposition. As a consequence, the percentage of zinc in the electroless Ni–Zn–P alloys never reaches high values. Using cyclic voltammetry the electrodeposition mechanism of Ni–Zn–P alloys was investigated. It was observed that the zinc deposition inhibits the nickel discharge and, as a consequence, its catalytic activity on hypophosphite oxidation. It was also found that increase in temperature or pH leads to the deposition of nickel rich alloys.
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    Microstructural characterization and corrosion resistance of Ni–Zn–P alloys electrolessly deposited from a sulphate bath (1999)
    Springer
    Journal of applied electrochemistry 29 (1999), S. 637-645 
    Details
    ISSN: 1572-8838
    Keywords: alloys ; electroless ; microstructure ; morphology ; nickel ; phosphorus ; zinc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Electroless Ni–Zn–P alloy coatings were obtained on an iron substrate from a sulfate bath at various pH values. The effects of changes in bath pH on alloy composition, morphology, microstructure and corrosion resistance were studied. Scanning electron microscopy was performed to observe the morphological change of the deposits with bath pH. Coating crystallinity was investigated by grazing incidence asymmetric Bragg X-ray diffraction and transmission electron microscopy. A transition from an amorphous to polycrystalline structure was observed on increasing the bath alkalinity, and thus decreasing the phosphorus content of the alloys. A single crystalline phase corresponding to face-centred-cubic nickel was identified in the alloys obtained from a strong alkaline solution. An increase in zinc percentage up to 23% in the deposits does not change the f.c.c. nickel crystalline structure. Corrosion potential and polarization resistance measurements indicated that the corrosion resistance of electroless Ni–Zn–P alloys depends strongly on the microstructure and chemical composition. The deposits obtained at pH 9.0–9.5 and with 11.4–12.5% zinc and 11.8–11.2% phosphorous exhibited the best corrosion resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026441403282
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    Effects of repeated manure and fertilizer phosphorus additions on soil phosphorus dynamics under a soybean-wheat rotation (1999)
    Springer
    Biology and fertility of soils 28 (1999), S. 150-155 
    Details
    ISSN: 1432-0789
    Keywords: Key words Phosphorus dynamics ; Olsen ; phosphorus ; Soil phosphorus fractions ; Manure ; Soybean-wheat rotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract  Soil P availability and efficiency of applied P may be improved through an understanding of soil P dynamics in relation to management practices in a cropping system. Our objectives in this study were to evaluate changes in plant-available (Olsen) P and in different inorganic P (Pi) and organic P (P0) fractions in soil as related to repeated additions of manure and fertilizer P under a soybean-wheat rotation. A field experiment on a Typic Haplustert was conducted from 1992 to 1995 wherein the annual treatments included four rates of fertilizer P (0, 11, 22 and 44 kg ha–1 applied to both soybean and wheat) in the absence and presence of 16 t ha–1 of manure (applied to soybean only). With regular application of fertilizer P to each crop the level of Olsen P increased significantly and linearly through the years in both manured and unmanured plots. The mean P balance required to raise Olsen P by 1 mg kg–1 was 17.9 kg ha–1 of fertilizer P in unmanured plots and 5.6 kg ha–1 of manure plus fertilizer P in manured plots. The relative sizes of labile [NaHCO3-extractable Pi (NaHCO3-Pi) and NaHCO3-extractable P0 (NaHCO3-P0)], moderately labile [NaOH-extractable Pi (NaOH-Pi) and NaOH-extractable P0 (NaOH-P0)] and stable [HCl-extractable P (HCl-P) and H2SO4/H2O2-extractable P (resisual-P)] P pools were in a 1 : 2.9 : 7.6 ratio. Application of fertilizer P and manure significantly increased NaHCO3-Pi and -P0 and NaOH-Pi, and -P0 fractions and also total P. However, HCl-P and residual-P were not affected. The changes in NaHCO3-Pi, NaOH-Pi and NaOH-P0 fractions were significantly correlated with the apparent P balance and were thought to represent biologically dynamic soil P and act as major sources and sinks of plant-available P.
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    URL: http://dx.doi.org/10.1007/s003740050477
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    Stable isotope (δ13C and δ15N) signatures of sedimented organic matter as indicators of historic lake trophic state (1999)
    Springer
    Journal of paleolimnology 22 (1999), S. 205-221 
    Details
    ISSN: 1573-0417
    Keywords: carbon isotopes ; diatoms ; lake management ; nitrogen isotopes ; phosphorus ; radium-226 ; sediments ; trophic state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract We explored the use of carbon and nitrogen isotopes (δ13C and δ15N) in sedimented organic matter (OM) as proxy indicators of trophic state change in Florida lakes. Stable isotope data from four 210Pb-dated sediment cores were compared stratigraphically with established proxies for historical trophic state (diatom-inferred limnetic total phosphorus, sediment C/N ratio) and indicators of cultural disturbance (sediment total P and 226Ra activity). Diatom-based limnetic total P inferences indicate a transition from oligo-mesotrophy to meso-eutrophy in Clear Lake, and from eutrophy to hypereutrophy in Lakes Parker, Hollingsworth and Griffin. In cores from all four lakes, the carbon isotopic signature of accumulated OM generally tracks trophic state inferences and cultural impact assessments based on other variables. Oldest sediments in the records yield lower diatom-inferred total limnetic P concentrations and display relatively low δ13C values. In the Clear, Hollingsworth and Parker records, diatom-inferred nutrient concentrations increase after ca. AD 1900, and are associated stratigraphically with higher δ13C values in sediment OM. In the Lake Griffin core, both proxies display slight increases before ~1900, but highest values occur over the last ~100 years. As Lakes Clear, Hollingsworth and Parker became increasingly nutrient-enriched over the past century, the δ15N of sedimented organic matter decreased. This reflects, in part, the increasing relative contribution of nitrogen-fixing cyanobacteria to sedimented organic matter as primary productivity increased in these waterbodies. The Lake Griffin core displays a narrow range of both δ13C and δ15N values. Despite the complexity of carbon and nitrogen cycles in lakes, stratigraphic agreement between diatom-inferred changes in limnetic total P and the stable isotope signatures of sedimented OM suggests that δ13C and δ15N reflect shifts in historic lake trophic state.
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    URL: http://dx.doi.org/10.1023/A:1008078222806
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    Calibration of diatoms along a nutrient gradient in Florida Everglades Water Conservation Area-2A, USA (1999)
    Springer
    Journal of paleolimnology 22 (1999), S. 413-437 
    Details
    ISSN: 1573-0417
    Keywords: diatoms ; Everglades ; phosphorus ; wetland ; calibration ; multivariate ; Florida
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract The relationship between diatom taxa preserved in surface soils and environmental variables at 31 sites in Water Conservation Area 2A (WCA-2A) of the Florida Everglades was explored using multivariate analyses. Surface soils were collected along a phosphorus (P) gradient and analyzed for diatoms, total P, % nitrogen (N), %carbon (C), calcium (Ca), and biogenic silica (BSi). Phosphorus varied from 315-1781 μg g-1, and was not found to be correlated with the other geochemical variables. Canonical correspondence analysis (CCA) was used to examine which environmental variables correlated most closely with the distributions in diatom taxa. Canonical correspondence analysis with forward selection, constrained and partial CCA, and Monte Carlo permutation tests of significance show the most significant changes in diatom assemblages along the P gradient (p 〈 0.01), with additional species differences correlated with soil C, N, Ca, and BSi. Weighted-averaging (WA) regression and calibration models of diatom assemblages to P and BSi were developed. The diatom-based inference model for soil [P] had a high apparent r2 (0.86) with RMSEboot = 218 μg g-1. Indicator diatom species identified by assessing species WA optima and WA tolerance to [P], such as Nitzschia amphibia and N. palea for high [P] (~1300-1400 μ g-1) and Achnanthes minutissima var. scotica and Mastogloia smithii for low [P] (~400-600 μg g-1), may be useful as monitoring tools for eutrophication in WCA-2A as well as other areas of the Everglades. Diatom assemblages analyzed by cluster analysis were related to location within WCA-2A, and dominant taxa within clusters are discussed in relation to the geochemical variables measured as well as hydrology and pH. Diversity of diatom assemblages and a ‘Disturbance Index’ based on diatom data are discussed in relation to the historically P-limited Everglades ecosystem. Diatom assemblages should be very useful for reconstructions of [P] through time in the Florida Everglades, provided diatoms are well preserved in soil cores.
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    URL: http://dx.doi.org/10.1023/A:1008049224045
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    Controlling soil water content in fertiliser dissolution experiments (1999)
    Springer
    Nutrient cycling in agroecosystems 55 (1999), S. 7-14 
    Details
    ISSN: 1573-0867
    Keywords: fertiliser formulation ; nutrients ; phosphorus ; relative humidity ; soil moisture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Phosphorus lost in runoff from agricultural land leads to the enrichment of surface waters and contributes to algal blooms. Fertilisers are one source of this P. To compare the water available P of different fertiliser formulations in the laboratory it is necessary to control environmental conditions, temperature, relative humidity and soil water content, prior to simulating rainfall. Two chambers were designed in which relative humidity and soil water content were controlled using salt solutions. An initial design comprising a sealed chamber with three layers of soil samples over a salt bath was found to be inferior to a single layer design. The changes in water content of soil samples were used to test the single layer chamber in a constant temperature environment (15 °C) using a saturated KCl solution (90% relative humidity). Based on the final soil water content of the samples, the spatial variation within the chamber was within tolerable limits. The single layer chamber was used for a simulation experiment comparing the water available P of two commercial fertilisers. Using a saturated resorcinol solution (95% relative humidity) soil samples were equilibrated at 15 °C for 21 days, fertiliser added, and the water available P measured up to 600 h after fertiliser application. The results indicate that the amount of water available P was related to the fertiliser compound and exponentially related to the time since fertiliser application. It was concluded that the single layer chamber is suitable for controlling relative humidity and soil water content in trials such as these where the water available P of fertilisers are being compared.
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    URL: http://dx.doi.org/10.1023/A:1009816716466
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    Transfers of phosphorus within three dairy farming systems receiving varying inputs in feeds and fertilizers (1999)
    Springer
    Nutrient cycling in agroecosystems 55 (1999), S. 63-75 
    Details
    ISSN: 1573-0867
    Keywords: dairy systems ; feeds ; fertilizers ; phosphorus ; P surplus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Inputs of phosphorus (P) above requirements for production on dairy farms lead to surplus P with increased risk of P transfer in land run-off to surface waters causing eutrophication. The impact of reducing surplus P inputs in purchased feeds and fertilizers on milk and forage production was investigated in a comparison of three dairy farm systems on chalkland soils in southern England over a 3-year period. In accordance with current commercial practice, no attempt was made to regulate P inputs in system 1, which accumulated an average annual surplus of 23 kg P ha-1. Progressive reductions in purchased feed and/or fertilizer inputs into systems 2 and 3 decreased surplus P to 17 and 3 kg ha-1, respectively, without apparently limiting either milk or herbage dry matter production. The estimated reduction in faecal P output from system 3 cows fed a low P diet compared to system 1 cows fed a high P diet was 26%. Milk P concentrations significantly (P 〈0.001) increased in systems 2 and 3 which included maize in the diet. Output of P in milk and meat products, as a proportion of the total dietary P inputs, increased from 28% in system 1 to 36% in system 3. Surplus P was greatest in continuous maize fields receiving both dairy manure and starter P fertilizer. Withholding P fertilizer in system 3 did not reduce P offtake in cut herbage on soils of moderate P fertility. Total annual losses of P in storm run-off and leaching were no greater than annual inputs of P from the atmosphere (0.5 kg ha-1). The results indicate there is scope to reduce surplus P on commercial dairy farms without sacrificing production targets at least in the short term. Purchased feeds are the largest of the P inputs on intensive dairy farms, yet these are rarely quantified on commercial holdings.
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    URL: http://dx.doi.org/10.1023/A:1009860915462
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    Applications of poultry litter and triple superphosphate fertilizer to a sandy soil: effects on soil phosphorus status and profile distribution (1999)
    Springer
    Nutrient cycling in agroecosystems 54 (1999), S. 233-242 
    Details
    ISSN: 1573-0867
    Keywords: leaching ; phosphorus ; poultry litter ; soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract To determine P loadings, added through poultry litter, sufficient to cause downward movement of P from the cultivated layer of a sandy soil, six rates of poultry litter were applied annually for four years to a site in central England. (total loading 0 – 1119 kg P ha-1). A single extra plot also received an extra 1000 kg ha-1 as triple superphosphate (TSP; total loading 2119 kg P ha-1) and three other treatments received 200 – 800 kg ha-1 P as TSP only. Annual soil sampling in 30-cm increments to 1.5-m depth provided information on P build-up in the topsoil and P movement to depth. There were strong linear trends between P balance (P applied – P removed in crops) and total P, Olsen bicarbonate extractable P and water-soluble P in the topsoil. Phosphorus from TSP and poultry litter fell on the same regression lines, suggesting that both would be equally effective as fertilizer sources. We calculated that 100 kg ha-1 surplus total P would increase the Olsen extractable P content by c. 6 mg kg-1 and the water-soluble P by c. 5 mg kg-1. Thus, relatively large amounts of P would need to be applied to raise soil P status. We found some evidence of P movement into the soil layers immediately below cultivation depth. However, neither soil sampling nor soil solution extracted through Teflon water samplers showed evidence of movement into the deep subsoil (1 m) despite large P loadings.
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    Inorganic phosphorus and manure effects on bahiagrass production on a Spodosol (1999)
    Springer
    Nutrient cycling in agroecosystems 54 (1999), S. 259-266 
    Details
    ISSN: 1573-0867
    Keywords: bahiagrass ; manure ; pasture fertilization ; phosphorus ; phosphorus cycling ; Spodosol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Bahiagrass (Paspalum notatum Flugge) pasture fertilization recommendations have traditionally been based upon clipping studies. Inclusion of P from manure, not originally considered when P recommendations were developed for pastures, may minimize the need for P fertilization without reducing bahiagrass production or P uptake. The objective of this research was to determine if manure contributes greatly to the P crop nutrient requirement. A 2-year field study utilized a factorial arrangement of 0 and 6.9 Mg air-dried manure ha-1 with 0, 17, 34, 51, and 68 kg inorganic P ha-1 from triple superphosphate to evaluate bahiagrass yield, root distribution, and P uptake response on a Myakka fine sand (sandy, siliceous, hyperthermic Aeric Alaquod). Because air-dried manure was used in the field study, a greenhouse study was employed to confirm that there were no differences in bahiagrass yield or P uptake from either air-dried or fresh cattle (Bos spp.) manure sources. There were no manure or manure by P interaction effects on yield or P uptake of bahiagrass indicating that manure source did not effect grass production in the greenhouse. In the field study, bahiagrass roots were distributed into the Bh horizon, and the Bh horizon had at least four times more Mehlich-1 extractable P than that of the Ap horizon. This horizon was most likely acting as a main source for P-uptake by the grass. This observation was further confirmed by no yield response to levels of inorganic P application in 1989. A linear-response-and-plateau (R2=0.196) relationship with a critical point of 15.4 kg P ha-1 was found in 1990. Bahiagrass yield and P uptake were not dependent on P fertilization, either from manure or inorganic P, due to the availability of P from the Bh horizon.
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    URL: http://dx.doi.org/10.1023/A:1009831011649
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    Nucleotide sequences of three distinct complementary DNA clones encoding rat class II major histocompatibility complex RT1.D β-chain proteins (1999)
    Springer
    Immunogenetics 49 (1999), S. 735-737 
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    ISSN: 1432-1211
    Keywords: Key words Class II MHC sequence ; Rat ; Cloning ; RT-PCR ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/s002510050676
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    Cytokine-induced conversion of mesencephalic-derived progenitor cells into dopamine neurons (1999)
    Springer
    Cell & tissue research 296 (1999), S. 235-246 
    Details
    ISSN: 1432-0878
    Keywords: Key words Transplantation ; Parkinson’s disease ; CNS fetal development ; CNS differentiation ; Neurotrophic factors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have previously shown that a combination of the cytokines interleukin (IL)-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) can convert rat fetal (E14.5) mesencephalic progenitor cells into tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in vitro. The experiments described here characterize the mesencephalic progenitor cells and their cytokine-induced conversion into dopamine (DA) neurons. For all experiments, we used bromodeoxyuridine (BrdU)-ir cultures of (E14.5) mesencephalic progenitor cells that had been expanded at least 21 days. We first demonstrated that IL-1 induced DA neuron conversion in mesencephalic progenitors, but not in striatal progenitors (P〈0.001). Thus, these cells should be classified as lineage-restricted progenitors, and not omnipotent stem cells. To further characterize cell populations in these cultures, we used monoclonal antibodies against Hu (an early marker for neurons), growth-associated protein (GAP)-43 (a marker for neuronal process extension), TH (a marker for DA neurons), and glial fibrillary acidic protein (GFAP, a marker for astrocytes). We assessed (E14.5) mesencephalic progenitor cell cultures (plated at 125,000 cells/cm2) incubated in the cytokine mixture (described above) or in complete media (CM, negative control). Following 7 days incubation, GFAP-positive cells formed a nearly confluent carpet in both types of cultures. However, numbers of Hu-ir and GAP-43-ir cells in the cytokine-incubated cultures far exceeded those in CM-incubated controls (P=0.0003, P=0.0001, respectively), while numbers of TH-ir cells were 58-fold greater in the cytokine-incubated cultures versus CM-incubated controls. The TH phenotype persisted for 7 days following withdrawal of the differentiation media. Numerous double-labeled cells that were BrdU-ir and also TH-ir, or Hu-ir and also TH-ir, were observed in the cytokine-incubated cultures. These data suggest that cytokines ”drive” the conversion of progenitor cells into DA neurons.
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    Isograft and xenograft of the subcommissural organ into the lateral ventricle of the rat and the formation of Reissner’s fiber (1999)
    Springer
    Cell & tissue research 296 (1999), S. 457-469 
    Details
    ISSN: 1432-0878
    Keywords: Key words Subcommissural organ ; Isograft ; Xenograft ; Reissner’s fiber ; Cerebrospinal fluid ; Rat ; Bovine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The subcommissural organ (SCO) secretes glycoproteins into the cerebrospinal fluid (CSF) that aggregate and form Reissner’s fiber (RF). The factors involved in this aggregation are not known. One factor may be the hydrodynamics of the CSF when flowing through the aqueduct. This hypothesis was tested by isografting rat SCO and xenografting bovine SCO into the lateral ventricle of rats. Xenografts were either fresh bovine SCO or explants cultured for 30 days before transplantation. The grafts were investigated by electron microscopy and immunocytochemistry using antibodies against RF glycoproteins, serotonin and the glucose transporter I. Maximal time of transplantation was 43 days for isografts and 14 days for xenografts. The isografts were not reinnervated but were revascularized; they secreted into the ventricle RF glycoproteins that became progressively packed into pre-RF and RF structures identical to those formed by the SCO in situ. RF was confined to the host ventricle and at its distal end the constituent proteins disassembled. Xenografts were neither reinnervated nor revascularized and secreted into the host ventricle a material that never formed an RF. These findings indicate that the CSF factor responsible for the formation of RF is species specific, and that this process does not depend on the hydrodynamics of the CSF. The blood vessels revascularizing the isografted SCO acquired the characteristics of the vessels irrigating the SCO in situ, namely, a tight endothelium displaying glucose transporter I, and a perivascular space containing long-spacing collagen, thus indicating that basal release of glycoproteins may also occur in the grafted SCO.
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    Axonal and dendritic transport in Purkinje cells of cerebellar slice cultures studied by microinjection of horseradish peroxidase (1999)
    Springer
    Cell & tissue research 295 (1999), S. 55-64 
    Details
    ISSN: 1432-0878
    Keywords: Key words Axonal transport ; Purkinje cell ; Organotypic culture ; Microinjection ; Antimitotic drugs ; Cytoskeleton ; Dendritic transport ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Axonal and dendritic transport in single Purkinje neurons of cerebellar slice cultures was quantified as single transport distances. Examination of the cells within a vital tissue was regarded as being an approach to the in situ condition. The Purkinje cells were organotypically integrated in the in vitro tissues and extended long axonal projections connecting synapses to the target neurons. The tracer horseradish peroxidase (HRP) was applied via microinjection to the somata of the Purkinje cells and the injected neurons were incubated thereafter for defined time-intervals. The tracer was transported anterogradely into the neuron processes. The measurements on both the axonal and the dendritic transport of microinjected HRP revealed continuous transportation with increasing times of postincubation. This transport was reduced by the use of microtubule-depolymerizing drugs. The axonal transport of the tracer was either retarded in colchicine-treated cells or continuously reduced for up to 50% in vinblastine-treated neurons. Thus, a correlation of axonal transport to the microtubules was demonstrated. The dendrites were filled with the tracer after 60 min of postincubation. Dendritic transport was reduced by the use of vinblastine, and not significantly by colchicine. The results strongly support the dependence of neuronal transport on microtubules as a component of the cytoskeleton.
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    Cellular and subcellular distribution of the calcium-binding protein NCS-1 in the central nervous system of the rat (1999)
    Springer
    Cell & tissue research 295 (1999), S. 395-407 
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    ISSN: 1432-0878
    Keywords: Key words Neurofilament ; Basket cell ; Pinceau ; Golgi apparatus ; Calcium binding protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract NCS-1 (neuronal calcium sensor) is a recently characterized member of a highly conserved neuron-specific family of calcium-binding proteins, which also includes frequenin and recoverin. The cellular and subcellular distributions of NCS-1 in the rat nervous system were investigated using light- and electron-microscopic immunohistochemistry. NCS-1 immunoreactivity was localized to neuronal cell bodies and axons throughout the brain and spinal cord but not to glial cells. The most intense labeling was observed in myelinated axons, the axonal ramifications of the basket cell in the cerebellar cortex, and large neurons in the brainstem and pons. These same structures were also characterized by heavy labeling for neurofilament protein, as determined by double-labeling experiments. Most axon terminals were unlabeled or only lightly labeled. The most remarkable subcellular staining occurred in the perikarya where intense labeling was associated with the membranes of the trans saccules of the Golgi apparatus. The widespread distribution of NCS-1 indicates that it may be active in a variety of calcium-dependent neuronal functions, whereas the specific subcellular localization to the Golgi apparatus and neurofilament-rich structures suggests a specialized role in calcium regulated protein trafficking and cytoskeletal interactions.
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    Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue (1999)
    Springer
    Cell & tissue research 295 (1999), S. 467-475 
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    ISSN: 1432-0878
    Keywords: Key words Glial cell line-derived neurotrophic factor ; GDNF ; Ret ; GDNFR-α ; Brain-derived neurotrophic factor ; BDNF ; NT-3 ; NT-4 ; trk receptors ; Thyroid tissue ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-α) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-α and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-α and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-α expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-α. This differential distribution of the GDNF receptor components (GDNFR-α and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.
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    Aquaporin-5 (AQP5), a water channel protein, in the rat salivary and lacrimal glands: immunolocalization and effect of secretory stimulation (1999)
    Springer
    Cell & tissue research 295 (1999), S. 513-521 
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    ISSN: 1432-0878
    Keywords: Key words Water channel protein ; Aquaporin ; AQP5 ; Rat ; Salivary glands ; Immunolocalization ; Secretory stimulation ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Aquaporin-5 (AQP5) is a water channel protein and is considered to play an important role in water movement across the plasma membrane. We raised anti-AQP5 antibody and examined the localization of AQP5 protein in rat salivary and lacrimal glands by immunofluorescence microscopy. AQP5 was found in secretory acinar cells of submandibular, parotid, and sublingual glands, where it was restricted to apical membranes including intercellular secretory canaliculi. In the submandibular gland, abundant AQP5 was also found additionally at the apical membrane of intercalated duct cells. Upon stimulation by isoproterenol, apical staining for AQP5 in parotid acinar cells tended to appear as clusters of dots. These results suggest that AQP5 is one of the candidate molecules responsible for the water movement in the salivary glands.
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    Retention of nutrients in river basins (1999)
    Springer
    Aquatic ecology 33 (1999), S. 29-40 
    Details
    ISSN: 1573-5125
    Keywords: denitrification ; nature restoration ; nitrogen ; phosphorus ; riparian areas ; sedimentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In Denmark, as in many other European countries, the diffuse losses of nitrogen (N) and phosphorus (P) from the rural landscape are the major causes of surface water eutrophication and groundwater pollution. The export of total N and total P from the Gjern river basin amounted to 18.2 kg ha−1 and 0.63 kg P ha−1 during June 1994 to May 1995. Diffuse losses of N and P from agricultural areas were the main nutrient source in the river basin contributing 76% and 51%, respectively, of the total export. Investigations of nutrient cycling in the Gjern river basin have revealed the importance of permanent nutrient sinks (denitrification and overbank sedimentation) and temporary nutrient storage in watercourses. Temporary retention of N and P in the watercourses thus amounted to 7.2–16.1 g N m−2 yr−1 and 3.7–8.3 g P m−2 yr−1 during low-flow periods. Deposition of P on temporarily flooded riparian areas amounted from 0.16 to 6.50 g P m−2 during single irrigation and overbank flood events, whereas denitrification of nitrate amounted on average to 7.96 kg N yr−1 per running metre watercourse in a minerotrophic fen and 1.53 kg N yr−1 per linear metre watercourse in a wet meadow. On average, annual retention of N and P in 18 Danish shallow lakes amounted to 32.5 g N m−2 yr−1 and 0.30 g P m−2 yr−1, respectively, during the period 1989–1995. The results indicate that permanent nutrient sinks and temporary nutrient storage in river systems represent an important component of river basin nutrient budgets. Model estimates of the natural retention potential of the Gjern river basin revealed an increase from 38.8 to 81.4 tonnes yr−1 and that P-retention increased from −0.80 to 0.90 tonnes yr−1 following restoration of the water courses, riparian areas and a shallow lake. Catchment management measures such as nature restoration at the river basin scale can thus help to combat diffuse nutrient pollution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009947907811
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  • 96
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    Electronic Resource
    Variation in nutrient availability and plant species diversity across forb and graminoid zones of a Northern New England high salt marsh (1999)
    Springer
    Plant ecology 143 (1999), S. 219-228 
    Details
    ISSN: 1573-5052
    Keywords: mineralization ; nitrogen ; phosphorus ; salinity ; stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Plant zonation patterns across New England salt marshes have been investigated for years, but how nutrient availability differs between zones has received little attention. We investigated how N availability, P availability, and plant N status varied across Juncus gerardii, Spartina patens, and mixed forb zones of a Northern New England high salt marsh. We also investigated relationships between several edaphic factors and community production and diversity across the high marsh. P availability, soil salinity, and soil moisture were higher in the mixed forb zone than in the two graminoid zones. NH+ 4-N availability was highest in the J. gerardii zone, but NO− 3-N availability and mid season net N mineralization rates did not vary among zones. Plant tissue N concentrations were highest in the mixed forb zone and lowest in the S. patens zone, reflecting plant physiologies more so than soil N availability. Community production was highest in the J. gerardii zone and was positively correlated with N availability and negatively correlated with soil moisture. Plant species diversity was highest in the mixed forb zone and was positively correlated with P availability and soil salinity. Thus, nutrient availability, plant N status, and plant species diversity varied across zones of this high marsh. Further investigation is needed to ascertain if soil nutrient availability influences or is a result of the production and diversity differences that exist between vegetation zones of New England high salt marshes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009887727465
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  • 97
    Electronic Resource
    Electronic Resource
    A human capecitabine excretion balance and pharmacokinetic study after administration of a single oral dose of 14C-labelled drug (1999)
    Springer
    Investigational new drugs 17 (1999), S. 49-56 
    Details
    ISSN: 1573-0646
    Keywords: pharmacokinetics ; capecitabine ; 5-fluorouracil ; phase I trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract An excretion balance and pharmacokinetic study was conducted in cancer patients with solid tumors who received a single oral dose of capecitabine of 2000 mg including 50 μ Ci of 14C-radiolabelled capecitabine. Blood, urine and fecal samples were collected until radioactive counts had fallen to below 50 dpm/mL in urine, and levels of intact drug and its metabolites were measured in plasma and urine by LC/MS-MS (mass spectrometry) and 19F-NMR (nuclear magnetic resonance) respectively. Based on the results of the 6 eligible patients enrolled, the dose was almost completely recovered in the urine (mean 95.5%, range 86–104% based on radioactivity measurements) over a period of 7 days after drug administration. Of this, 84% (range 71–95) was recovered in the first 12 hours. Over this time period, 2.64% (0.69–7.0) was collected in the feces. Over a collection period of 24–48h, a total of 84.2% (range 80–95) was recovered in the urine as the sum of the parent drug and measured metabolites (5′-DFCR, 5′-DFUR, 5-FU, FUH2, FUPA, FBAL). Based on the radioactivity measurements of drug-related material, absorption is rapid (tmax 0.25–1.5 hours) followed by a rapid biphasic decline. The parent drug is rapidly converted to 5-FU, which is present in low levels due to the rapid metabolism to FBAL, which has the longest half-life. There is a good correlation between the levels of radioactivity in the plasma and the levels of intact drug and the metabolites, suggesting that these represent the most abundant metabolites of capecitabine. The absorption of capecitabine is rapid and almost complete. The excretion of the intact drug and its metabolites is rapid and almost exclusively in the urine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006263400888
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  • 98
    Electronic Resource
    Electronic Resource
    A Sensitive Docetaxel Assay in Plasma by Solid-Phase Extraction and High Performance Liquid Chromatography – UV Detection: Validation and Suitability in Phase I Clinical Trial Pharmacokinetics (1999)
    Springer
    Investigational new drugs 17 (1999), S. 325-333 
    Details
    ISSN: 1573-0646
    Keywords: docetaxel ; plasma assay ; clinical trials ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have developed a specific and sensitive method aiming atdocetaxel (Taxotere®) determination in plasma of treatedpatients. This involved solid-phase extraction of 1 ml of plasmaonto carboxylic acid (CBA) grafted silica cartridges followed byreversed-phase liquid chromatography with UV detection. The bestselectivity was obtained through the use of C18 Uptisphere® asstationary phase. The low limit of quantitation obtained (LOQ:5 ng/ml) allowed measurements of docetaxel up to 24 hours afterone-hour infusions with low dosages of drug (60 mg/m2). Themethod was applied successfully to monitor docetaxel plasma levelswithin two protocols associating fixed dosages of either methotrexate or gemcitabine with escalating doses of Taxotere®.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006327302041
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  • 99
    Electronic Resource
    Electronic Resource
    Effect of meteorology and nutrient load on oxygen depletion in a Danish micro-tidal estuary (1999)
    Springer
    Aquatic ecology 33 (1999), S. 55-64 
    Details
    ISSN: 1573-5125
    Keywords: estuaries ; nitrogen ; oxygen depletion ; phosphorus ; regression model ; vertical mixing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In a detailed analysis of oxygen saturation in a shallow Danish estuary it was possible to separate the effect of meteorological forcings (i.e. wind and solar radiation) and nutrient loads on oxygen depletion in bottom water. Regression analysis showed that oxygen saturation tied to nitrogen load rather than to phosphorus load. During summer periods of stratification the oxygen saturation could be attributed to the time elapsed after the onset of stratification and the accumulated nitrogen loading 10 month prior to measurement. Using a 10-year meteorological database and an empirical model it was calculated that a 25% reduction in nitrogen loading would reduce the number of days with severe oxygen depletion (i.e. 〈15% of saturation) by more than 50%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009956210537
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  • 100
    Electronic Resource
    Electronic Resource
    Application of a Combined “Effect Compartment/Indirect Response Model” to the Central Nervous System Effects of Tiagabine in the Rat (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 301-323 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacodynamics ; effect compartment model ; indirect response ; sigmoid E max ; tiagabine ; GABA uptake inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacological inhibition of GABA uptake transporters provides a mechanism for increasing GABAergic transmission, which may be useful in the treatment of various neurological disorders. The purpose of our investigations was to develop an integrated pharmacokinetic–pharmacodynamic (PK/PD) model for the characterization of the pharmacological effect of tiagabine, R-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl)nipecotic acid, in individual rats in vivo. The tiagabine-induced increase in the amplitude of the EEG 11.5–30 Hz frequency band (β), was used as pharmacodynamic endpoint. Chronically instrumented male Wistar rats were randomly allocated to four groups which received an infusion of 3, 10, or 30 mg kg −1 $$(\bar x \pm SE,{\text{ }}n = 23)$$ $$96 \pm 9$$ ml min -1 kg−1, 1.5ŷ0.1 L kg−1 and 20ŷ0.2 min.A time delay was observed between the occurrence of maximum plasma drug concentrations and maximal response. A physiological PK/PD model has been used to account for this time delay, in which a biophase was postulated to account for tiagabine available to the GABA uptake carriers in the synaptic cleft and the increase in EEG effect was considered an indirect response due to inhibition of GABA uptake carriers. The population values for the pharmacodynamic parameters characterizing the delay in pharmacological response relative to plasma concentrations were keo=0.030 min −1 and kout=81 min−1, respectively. Because of the large difference in these values the PK/PD model was simplified to the effect compartment model. Population estimates $$(\bar x \pm SE)$$ were E0=155 ŷ 6 μV, Emax=100 ŷ 5 μV, EC50=287 ŷ 7 ng ml−1, Hill factor=1.8 ŷ 0.2 and keo=0.030 ŷ 0.002 min −1. The results of this analysis show that for tiagabine the combined “effect compartment-indirect response” model can be simplified to the classical “effect compartment” model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020999114109
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