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  • pharmacokinetics  (2.025)
  • Rat  (826)
  • wheat  (807)
  • Inversion
  • Springer  (3.693)
  • American Geophysical Union  (2)
  • Institut für Meteorologie und Geophysik  (2)
  • Wiley  (2)
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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
    Publikationsdatum: 2022-05-25
    Beschreibung: 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.
    Beschreibung: 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.
    Beschreibung: This research is supported by the National Aeronautics and Space Administration contracts NNX08AT77G, NNX06AC75G, and NNX08AM56G.
    Schlagwort(e): Atmospheric transport ; Carbon cycle ; Inversion ; Isentropic coordinates ; Synoptic weather ; Tracer modeling
    Repository-Name: Woods Hole Open Access Server
    Materialart: Article
    Format: application/pdf
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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
    Publikationsdatum: 2022-05-26
    Beschreibung: 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.
    Beschreibung: 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.
    Beschreibung: This material is based upon work supported by the National Science Foundation under grant OCE‐0402363 and Department of Energy grant DE‐FG02‐08ER64619.
    Schlagwort(e): Inversion ; MOC ; Abrupt ; Sea level ; Coral ; Mixing
    Repository-Name: Woods Hole Open Access Server
    Materialart: 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
    Publikationsdatum: 2017-04-04
    Beschreibung: 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.
    Beschreibung: Published
    Beschreibung: 251-266
    Beschreibung: 2.6. TTC - Laboratorio di gravimetria, magnetismo ed elettromagnetismo in aree attive
    Beschreibung: 3.4. Geomagnetismo
    Beschreibung: 3.5. Geologia e storia dei sistemi vulcanici
    Beschreibung: JCR Journal
    Beschreibung: reserved
    Schlagwort(e): 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)
    Materialart: article
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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
    Publikationsdatum: 2002
    Schlagwort(e): Inversion ; Data analysis / ~ processing ; Non-linear effects ; Discrimination ; C&G
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    BIBLIOGRAFIE SEISMOLOGIE
  • 5
    Digitale Medien
    Digitale Medien
    Kegelschnittbüschel und Inversion (2000)
    Springer
    Geometriae dedicata 83 (2000), S. 31-37 
    Details
    ISSN: 1572-9168
    Schlagwort(e): Vollständiges Viereck ; Kegelschnittbüschel ; Konjugiertheitsabbildung ; Inversion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Mathematik
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1005294714649
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  • 6
    Digitale Medien
    Digitale Medien
    Simultaneous Records of Methane and Nitrous Oxide Emissions in Rice-Based Cropping Systems under Rainfed Conditions (2000)
    Springer
    Nutrient cycling in agroecosystems 58 (2000), S. 131-139 
    Details
    ISSN: 1573-0867
    Schlagwort(e): automated closed chamber method ; wheat ; cowpea ; slow-release nitrogen fertilizer ; residue management ; denitrification ; methane sink ; rainfall
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Rainfed rice (Oryza sativa L.)-based cropping systems are characterized by alternate wetting and drying cycles as monsoonal rains come and go. The potential for accumulation and denitrification of NO3 − is high in these systems as is the production and emission of CH4 during the monsoon rice season. Simultaneous measurements of CH4 and N2O emissions using automated closed chamber methods have been reported in irrigated rice fields but not in rainfed rice systems. In this field study at the International Rice Research Institute, Philippines, simultaneous and continuous measurements of CH4 and N2O were made from the 1994 wet season to the 1996 dry season. During the rice-growing seasons, CH4 fluxes were observed, with the highest emissions being in organic residue-amended plots. Nitrous oxide fluxes, on the other hand, were generally nonexistent, except after fertilization events where low N2O fluxes were observed. Slow-release N fertilizer further reduced the already low N2O emissions compared with prilled urea in the first rice season. During the dry seasons, when the field was planted to the upland crops cowpea [Vigna unguiculata (L.) Walp] and wheat (Triticum aestivum L.), positive CH4 fluxes were low and insignificant except after the imposition of a permanent flood where high CH4 fluxes appeared. Evidences of CH4 uptake were apparent in the first dry season, especially in cowpea plots, indicating that rainfed lowland rice soils can act as sink for CH4 during the upland crop cycle. Large N2O fluxes were observed shortly after rainfall events due to denitrification of accumulated NO3 −. Cumulative CH4 and N2O fluxes observed during this study in rainfed conditions were lower compared with previous studies on irrigated rice fields.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009842502608
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  • 7
    Digitale Medien
    Digitale Medien
    DC-resistivity mapping of internal landfill structures: two pre-excavation surveys (2000)
    Springer
    Environmental geology 39 (2000), S. 360-371 
    Details
    ISSN: 1432-0495
    Schlagwort(e): Key words Environmental geophysics ; Resistivity ; Inversion ; Landfill mining ; Waste ; Characterization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geologie und Paläontologie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002540050015
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  • 8
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002510050623
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  • 9
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s00418-004-0708-7
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  • 10
    Digitale Medien
    Digitale Medien
    Pharmacology of Fluorinated Pyrimidines: Eniluracil (2000)
    Springer
    Investigational new drugs 18 (2000), S. 373-381 
    Details
    ISSN: 1573-0646
    Schlagwort(e): clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006453500629
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  • 11
    Digitale Medien
    Digitale Medien
    Development of a STS marker linked to a major locus controlling flour colour in wheat (Triticum aestivum L.) (2000)
    Springer
    Molecular breeding 6 (2000), S. 169-174 
    Details
    ISSN: 1572-9788
    Schlagwort(e): AFLP ; flour colour ; STS ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Flour colour is an important quality trait in the production of bread, noodles and other related end products. Current screening for flour colour in breeding programs requires several grams of flour to be milled. In order to screen large numbers of plants, a rapid PCR-based assay is required. We report here the conversion of a codominant AFLP marker linked to a major locus controlling flour colour in hexaploid wheat, to a sequence tagged site (STS) marker for use in marker-assisted selection (MAS). The two-allelic AFLP bands were cloned and sequenced to allow specific primers to be designed. The primers amplified bands of the expected size in the parental varieties and co-segregated with the original AFLP marker in the mapping population. The primers also amplified alleles of the expected size from the DNA of parental lines of two other related mapping populations. Cultivars that contributed to the pedigree of the original parent `Schomburgk' used to generate the mapping population were also screened to determine the origin of the `yellow' allele.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009638017859
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  • 12
    Digitale Medien
    Digitale Medien
    Allometric Pharmacokinetic Scaling: Towards the Prediction of Human Oral Pharmacokinetics (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 410-418 
    Details
    ISSN: 1573-904X
    Schlagwort(e): allometric scaling ; interspecies scaling ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007520818956
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  • 13
    Digitale Medien
    Digitale Medien
    In Vivo Absorption Properties of Orally Administered Recombinant Human Interleukin-11 (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 482-485 
    Details
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007545524408
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  • 14
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007561727948
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  • 15
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007543805947
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  • 16
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026414713509
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  • 17
    Digitale Medien
    Digitale Medien
    Confidence Interval Criteria for Assessment of Dose Proportionality (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1278-1283 
    Details
    ISSN: 1573-904X
    Schlagwort(e): bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026451721686
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  • 18
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007512617139
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  • 19
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007661209921
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  • 20
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007557207590
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  • 21
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007560500301
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  • 22
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007512426420
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  • 23
    Digitale Medien
    Digitale Medien
    Potential Role of P-Glycoprotein in Affecting Hepatic Metabolism of Drugs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 903-905 
    Details
    ISSN: 1573-904X
    Schlagwort(e): P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007570517183
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  • 24
    Digitale Medien
    Digitale Medien
    An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    Details
    ISSN: 1573-904X
    Schlagwort(e): in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007500910566
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  • 25
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1573-904X
    Schlagwort(e): α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007512832006
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  • 26
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007595725360
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  • 27
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Hippocampus ; Vigilance states ; Paired-pulse ; Dentate gyrus ; Dentate granule cells ; Evoked response ; Rat ; In vivo studies ; Perforant path ; Maturation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Technik allgemein
    Notizen: 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
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1114/1.261
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  • 28
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Heart ; Left ventricle ; LV contractility ; ESPVR ; Pig ; Rat ; Magnetic resonance imaging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Technik allgemein
    Notizen: 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
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1114/1.289
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  • 29
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Time–frequency analysis ; Coherence ; Cross correlation ; Nonstationary persistent signals ; Central pattern generator ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Technik allgemein
    Notizen: 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
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1114/1.1313775
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  • 30
    Digitale Medien
    Digitale Medien
    The influence of crop management on the water balance of lupin and wheat crops on a layered soil in a Mediterranean climate (2000)
    Springer
    Plant and soil 221 (2000), S. 239-251 
    Details
    ISSN: 1573-5036
    Schlagwort(e): drainage ; duplex soil ; evapotranspiration ; lupin ; waterlogging ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The influence of time of sowing and sowing density on evapotranspiration and drainage loss beneath wheat (Triticum aestivum cv. Spear) and lupin (Lupinus angustifolius cv. Gungurru) crops grown on a layered soil was investigated for three seasons in a Mediterranean climate in Western Australia. The aim of the study was to investigate whether managing crops to maximise their canopy growth would increase their water use and minimise groundwater recharge contributing to dryland salinity. A soil water balance approach was used to estimate evapotranspiration, with changes in soil water content measured with a neutron water meter. The study was carried out on a layered soil typical of agricultural soils in the region with variable depth to clay (0.22–0.38 m) and a marked contrast in hydraulic properties between the topsoil and subsoil. As a result of the low permeability subsoil, a perched water table occurred in the sandy topsoil in each of the three seasons under study during winter when rainfall was high and potential evaporation low. Perched water tables persisted for 2–3 months, with hydraulic gradients consistently downward causing drainage losses to occur. Although crop management had a large influence on shoot and root development, evapotranspiration from the different treatments was generally similar. Drainage losses were not influenced by either crop type, time of sowing or sowing density, because potential evaporation and hence evapotranspiration was low during the period when drainage losses occurred. The total drainage loss measured in each season was different, with losses ranging from 20.1 to 22.2 mm in 1990, from 40.4 to 46.7 mm in 1991 and from 49.4 to 66.6 mm in 1992. The increase in drainage loss from 1990 to 1992 was a result of progressively more seasonal rainfall in 1990, 1991 and 1992. It was concluded that there was little scope to increase water use and decrease deep drainage through crop management for sites with climatic conditions where winter rainfall exceeds potential evaporation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1004732706073
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  • 31
    Digitale Medien
    Digitale Medien
    Availability of different forms of sulphur fertilisers to wheat and oilseed rape (2000)
    Springer
    Plant and soil 222 (2000), S. 139-147 
    Details
    ISSN: 1573-5036
    Schlagwort(e): elemental sulphur ; oilseed rape ; sulphate ; sulphur fertilisers ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A pot experiment was conducted to compare the availability and efficiency of three sulphur (S) fertilisers to wheat in the first year and oilseed rape in the second year, using six agricultural soils. Four treatments were applied in the initial year: control (no S), two forms of elemental S (either micronised S° particles or a bentonite + S° mixture) and a sulphate fertiliser (ammonium sulphate). In the first year, the micronised S° was as effective as the sulphate fertiliser, both producing similar increases of wheat grain yield (on average 36%) and S uptake (on average 164%) over the control. In contrast, responses to the bentonite + S° form were minimal, indicating a limited S supply. In the second year the control treatment failed to produce seeds in most soils, whereas the micronised S° and sulphate treatments increased seed yields of oilseed rape to an average of 13.4 and 12.9 g pot-1, respectively. The performance of the bentonite + S° varied between soils: two soils produced yields similar to those of the other S fertilisers, while the remaining soils had low yields. To test whether the poor performance of the bentonite clay + S° fertiliser was due to the lack of exposure of the prills to physical weathering in the glasshouse, the effect of freeze-thaw action on the fertilisers performance was assessed in a separate pot experiment. The responses in wheat yield and S uptake showed that freeze-thaw did not enhance the physical disruption of the prills or fertiliser effectiveness. These results suggest that the release of available S from the bentonite + S° mixture was too slow to meet the requirement of wheat and oilseed rape.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1004757503831
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  • 32
    Digitale Medien
    Digitale Medien
    Colonization of wheat by Azospirillum brasilense Cd is impaired by saline stress (2000)
    Springer
    Plant and soil 225 (2000), S. 187-191 
    Details
    ISSN: 1573-5036
    Schlagwort(e): Azospirillum brasilense ; 2 ; 4-D ; para-nodules ; saline stress ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The effect of saline stress on the colonization of wheat was analyzed by using Azospirillum brasilense Cd carrying the fusion of the reporter gene lacZ (β-galactosidase) with the N2 fixation gene promoter nifA. Colonization was also studied by inducing para-nodules on wheat roots using 2,4-D, establishing that these structures acted as bacterium protected niches. Bacteria grown under standard conditions were distributed along the whole root system, except the elongation zone, and colonized the para-nodules. Bacteria experiencing saline stress were mainly localized at the root tips and the lateral roots. In 2,4-D treated plants, most of the bacteria were present around the basal surface of the modified lateral root structures. Using the MPN method, there were not statistical differences between the numbers of control and stressed bacteria. As this method estimates endophytic colonization in contrast with the one using X-gal, which emphasizes colonization on the root surface, both procedures demonstrated to be necessary, concluding that salt treatment reduced surface colonization (X-gal) but not colonization inside the root. The bacterial counts made on inoculated wheat roots indicated higher numbers of both control and stressed bacteria in roots treated with 2,4-D compared with untreated roots.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026516313021
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  • 33
    Digitale Medien
    Digitale Medien
    Selenium accumulation by sequentially grown wheat and rice as influenced by gypsum application in a seleniferous soil (2000)
    Springer
    Plant and soil 227 (2000), S. 243-248 
    Details
    ISSN: 1573-5036
    Schlagwort(e): residual effect of gypsum ; rice ; selenium toxicity ; sulphur ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A field experiment was conducted for 2 years on an alkaline calcareous seleniferous soil to study the effect of different levels of gypsum (0.2 – 3.2 t ha−1) applied to wheat only in the first year on Se accumulation by wheat (Triticum aestivum L.) – rice (Oryza sativa L.) cropping sequence. With gypsum application, grain yield of both rice and wheat crops increased by 0.4 – 0.5 t ha−1; the increase in straw yield was 0.4 – 1.1 t ha−1. Significant reduction in Se accumulation by wheat was observed with gypsum application up to 0.8 t ha−1 and its residual effect was evident on the following crops for 2 years. Reduction in Se accumulation varied from 53 to 64% in wheat grain, 46 to 49% in wheat straw, 35 to 63% in rice grain and 36 to 51% in rice straw with an application of gypsum at 0.8 t ha−1. A corresponding increase in S concentration was observed. In the gypsum-treated plots, the ratio of S:Se increased by 6 – 8 times in wheat and 3 – 6 times in rice. Reduction in Se accumulation by crop plants through gypsum application may help in lowering the risk of Se over-exposure of animals and humans that depend on diet materials grown on high selenium soils.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026579116794
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  • 34
    Digitale Medien
    Digitale Medien
    Genetic control of aluminum tolerance in mutant lines of the wheat cultivar Anahuac (2000)
    Springer
    Euphytica 114 (2000), S. 47-53 
    Details
    ISSN: 1573-5060
    Schlagwort(e): aluminum tolerance ; genetic control ; induced mutations ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The behavior of 17 gamma irradiation mutant lines derived from the aluminum sensitive wheat cultivar `Anahuac' was compared with two sensitive and three tolerant cultivars in nutritent solutions containing seven Al3+ concentrations (0; 0.5; 1; 2; 4; 6 and10 mg/liter), at a temperature of 25 °C and 4.0 pH. Tolerance was measured by the continued growth of the primary roots in a solution without aluminum after 48 hours in a solution containing a known concentration of aluminum. 14 mutant lines were as tolerant to the presence of 10 mg/liter of Al3+ in the treatment solutions as were the tolerant `BH-1146', `IAC-60' and `IAC-24' cultivars. Two mutant lines were tolerant and one was sensitive to the presence of 1 mg/liter of Al3+, while the cultivars `Siete Cerros' and `Anahuac' were sensitive to 1 and 0.5 mg/liter Al3+ in the solutions, respectively. F2 seedlings, obtained from cross among one sensitive and twelve tolerant mutant lines to the sensitive cultivars (`Siete Cerros' or `Anahuac') and the tolerant cultivars (`BH-1146' or `IAC-24') were assessed for tolerance to 2 mg/liter Al3+ in nutritient solutions. The twelve tolerant mutant lines and the tolerant `IAC-60' and `IAC-24' cultivars differed from the sensitive `Siete Cerros' or `Anahuac' cultivars by one pair of dominant alleles. The results indicated that tolerance in the induced mutants was due to a single pair of dominant alleles and that these alleles expressed the same tolerance as `BH-1146' and `IAC-24' cultivars.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003993320432
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  • 35
    Digitale Medien
    Digitale Medien
    Detection of wheat-barley translocations by genomic in situ hybridization in derivatives of hybrids multiplied in vitro (2000)
    Springer
    Euphytica 112 (2000), S. 117-123 
    Details
    ISSN: 1573-5060
    Schlagwort(e): barley ; GISH ; in situ hybridization ; translocation ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Wheat-barley translocations were identified by genomicin situ hybridization (GISH) in backcross progenies originating from in vitro regenerated wheat (Triticum aestivum L. cv. Chinese Spring) × barley (Hordeum vulgare L. cv. Betzes) hybrids. The regenerated hybrids were pollinated with the wheat line Martonvásári 9 kr1. Five translocated wheat-barley chromosomes were recovered among 51 BC2F2 progeny from the in vitro regenerated wheat × barley hybrids. All were single breakpoint translocations with the relative positions of the breakpoints ranging from the centromere to about 0.8 of the relative arm length. Of the four translocations with intercalary breakpoints, three were transfers of terminal barley segments to wheat chromosomes; one was a transfer of a terminal wheat segment to a barley chromosome. Because of the absence of diagnostic N-bands, the identity of three barley segments could not be determined; in one translocation the barley chromosome involved had a NOR so it must have been 5H or 6H, and the centric translocation was 4HS.2BL. Following selfing, homozygotes of four translocations were selected. The experiment suggests that in vitro culture conditions are conducive for major genome rearrangements in wheat-barley hybrids.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003840200744
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  • 36
    Digitale Medien
    Digitale Medien
    Epicuticular waxes and regulation of ear wetting and pre-harvest sprouting in barley and wheat (2000)
    Springer
    Euphytica 112 (2000), S. 157-166 
    Details
    ISSN: 1573-5060
    Schlagwort(e): barley ; cer ; β-diketone ; glaucous ; pre-harvest sprouting ; waxes ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Morphological features of the cereal ear, including awns, alter pre-harvest sprouting damage by changing the rate of water absorption during rainfall. In this paper, the potential for wheat (Triticum sp.) arid barley (Hordeum vulgare L.) waxes to reduce sprouting by increasing water repellency of the mature ear has been examined. Six barley F2 populations segregating for different non-glaucous single-gene mutants controlling waxes on ears were examined. Water repellency was assessed by measuring both the contact angle of a water drop placed on the lemma surface (internal angle) and by repetitive weighings of whole ears during their exposure to simulated rainfall. The lemma of glaucous (wild type) lines had larger water drop contact angles, an indication of poorer spread of water over the surface. In simulated rainfall, ears of the glaucous lines showed a clear reduction of wetting (20–30% less) and, after 72 h of wetting, their in-ear sprouting was reduced by 50 to 65%. When pre-wet, the glaucous ears also shed water more readily when shaken to simulate the combined effect of wind and rainfall. To reduce pre-harvest sprouting of barley it may be possible to screen visually for ears that are more glaucous but a more specific screen would be to select for lemma water drop contact angle since it is a good indicator of ear wettability and so allows differences in surface properties to be assessed. For bread wheat (T. aestivumL.), as for barley, the more glaucous the ear, the greater the water drop contact angle and the more tubular surface wax coverage seen in scanning electron microscope images. In addition, surface wax amount apparently affected in-ear wettingin lines of durum wheat, (T. turgidum L.). Possible genetic relationships between waxy/waxless genes in wheat and barley are suggested with the aim, ultimately, of altering ear glaucousness to give increased water repellency and a reduction of in-ear sprouting of wheat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003832031695
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  • 37
    Digitale Medien
    Digitale Medien
    Cross prediction in bread wheat germplasm using single seed descent lines (2000)
    Springer
    Euphytica 113 (2000), S. 65-70 
    Details
    ISSN: 1573-5060
    Schlagwort(e): cross prediction ; grain yield ; recombinant inbred lines ; single seed descent ; wheat ; yellow rust
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Populations of F6 recombinant inbred lines, generated by single seed descent from a half diallel among eight bread wheat lines adapted to the East African highlands, were used to identify those crosses that were more likely to produce cultivars which combined resistance to yellow rust with improved yield. Crosses having the most resistant line as one parent offered the best prospect of success, particularly those which produced F1hybrids exhibiting better parent heterosis. For plot grain yield there was a highly significant correlation between the observed and predicted rankings of the recombinant inbred line populations for the proportion of individual lines equalling or surpassing the target value. For yellow rust severity, however, this correlation was non-significant when a target value of zero was used. Adopting a slightly less stringent target of 0.25, coupled with the omission of two aberrant populations, increased this correlation significantly. The plant breeding implications of these results are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003985429998
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  • 38
    Digitale Medien
    Digitale Medien
    Evaluation of grain yield and its components in wheat cultivars and landraces under near optimal and drought conditions (2000)
    Springer
    Euphytica 113 (2000), S. 43-52 
    Details
    ISSN: 1573-5060
    Schlagwort(e): cultivars ; drought stress ; droughtsusceptibility index ; landraces ; wheat ; yield
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract In a 2-years experiment, 30 wheat cultivars and 21 landraces from different countries were tested under near optimum and drought stress conditions. Plant height, number of sterile spikelets per spike, spikelets per spike, number of kernels per spike, kernel weight per spike, 1000 kernel weight and grain yield were evaluated. The number of kernels per spike, 1000 kernel weight and especially yield were more sensitive to drought stress in the cultivars than plant height and number of spikelets per spike, while in the landraces these traits did not differ under drought stress compared to near optimum conditions. The average yield of cultivars was significantly better than the average yield of landraces under near optimum as well as drought stress conditions. Path coefficient analysis showed that for cultivars under near optimum conditions there was no significant direct association of any of the analysed characters with yield, while under drought stress conditions, number of kernels per spike had a significant positive direct effect. Under drought stress conditions, the number of sterile spikelets displayed a negative direct effect, while kernel weight per spike had a positive direct effect on yield. Hierarchical cluster analysis was used as a tool to classify cultivars and landraces according to their yield ability under near optimum and drought stress conditions. Among the cultivars, two groups out of five and among one of three in the landraces were characterised by high yields in both near optimum as well as under drought stress conditions. These genotypes may serve as sources of germplasm for breeding for drought tolerance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003997700865
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  • 39
    Digitale Medien
    Digitale Medien
    Comparative response of wheat and oilseed rape to nitrogen supply: absorption and utilisation efficiency of radiation and nitrogen during the reproductive stages determining yield (2000)
    Springer
    Plant and soil 220 (2000), S. 189-205 
    Details
    ISSN: 1573-5036
    Schlagwort(e): biomass ; intercepted radiation ; nitrogen nutrition ; oilseed rape ; radiation use efficiency ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract We investigated the response of spring wheat and oilseed rape to nitrogen (N) supply, focusing on the critical period for grain number definition and grain filling. Crops were grown in containers under a shelter and treated with five combinations of applied N. Wheat and oilseed rape produced comparable amounts of biomass and yield when corrected for the costs of biomass synthesis (SC). From the responses of biomass and yield to late N applications and the apparent contribution of mobilised biomass to yield, it seems that the yield of oilseed rape was more source-limited during grain filling than that of wheat, particularly at the medium and high N levels. Both species recovered equal amounts of N from the total available N in the soil and had similar N use efficiencies, expressed as yield per unit of N absorbed. However, oilseed rape had higher efficiency to convert absorbed N in biomass, but lower harvest index of N than wheat. Oilseed rape had similar or lower root biomass than wheat, depending on N level, but higher root length per unit soil volume and specific root length. The specific uptake rate of N per unit root dry weight during the critical period for grain number determination was higher in oilseed rape than in wheat. In wheat, N limitation affected growth through a similar or lower reduction in radiation use efficiency corrected for synthesis costs (RUESC) than in the cumulative amount of intercepted photosynthetically active radiation (IPARc). In oilseed rape, lower growth due to N shortage was associated more with RUESC than IPARc, during flowering while during grain filling both components contributed similarly to decreased growth. RUESC and the concentration of N in leaves and inflorescence (LIN%) decreased from flowering to maturity and were curvilinearly related. Oilseed rape tended to have higher RUESC than wheat at high N supply during the critical period for grain number determination, and generally lower during grain filling. The reasons for these differences and possibilities to increase yield potential are discussed in terms of the photosynthetic efficiency of the different organs and changes in source–sink ratio during reproductive stages.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1004757124939
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  • 40
    Digitale Medien
    Digitale Medien
    Improvement of resistance to Fusarium head blight by recurrent selection in an intermating breeding spring wheat population using the dominant male-sterile gene ms 2 (2000)
    Springer
    Euphytica 112 (2000), S. 79-88 
    Details
    ISSN: 1573-5060
    Schlagwort(e): Fusarium head blight ; intermating breedingpopulation ; male-sterile gene ms 2 ; recurrent selection ; resistance ; Triticum aestivum L. ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Four cycles of recurrent selection for FHB resistance were conducted in an intermating wheat breeding population using the dominant male-sterile gene ms 2 during 1987–1991.Five cycles of phenotypic mass selection for male-sterile plants were evaluated using the soil-surface inoculation method in Experiment I. Experiment II evaluated changes in FHB scores during five cycles of progeny selection for fertile plants using the single-floret inoculation method. In Experiment I, the average level of FHB response increased to MR level in C4, compared to MS level in C0. The numbers of infected spikelets and diseased kernels decreased 0.32 and 2.68 per cycle, respectively. In Experiment II, the average level of FHB response increased to R level in C4F1. The numbers of infected spikelets and diseased kernels decreased 0.93 and 4.58 per cycle, respectively. In both experiments, the largest selection gains were realized in the first cycle. The frequencies of R and MR individuals were increased significantly. The frequencies of individuals with FHB response equal and/or superior to Sumai 3 were increased to 5–8% in C4 and 25% in C4F1after the fourth cycle. Agronomic traits tended to be slightly improved in selected populations. Compared to 2% in C0, about 34% of lines superior in both FHB resistance and agronomic traits in C4F1 were selected to enter the conventional breeding program for further evaluation. Sixty three semidwarf lines superior in both FHB resistance and yield potential were selected from the F5 generations derived from C1F1 to C4F1. From them, two resistant cultivars with high-yielding potential were developed and commercialized in the Lower Yangtze Valley. Recurrent selection appears to be highly effective and feasible in shifting the average FHB response of the intermating population in the desirable direction, thereby enhancing the frequency of resistant individuals.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003850123088
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  • 41
    Digitale Medien
    Digitale Medien
    The inheritance and expression of grain texture in wheat, as measured by a microtome procedure (2000)
    Springer
    Euphytica 112 (2000), S. 261-265 
    Details
    ISSN: 1573-5060
    Schlagwort(e): grain texture ; microtome ; quality ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Although grain texture has been extensively studied, there is still some controversy about its mode of inheritance. The aim of this study was to use a microtome method to determine the inheritance of grain texture. The backcross method was used with a hard, well adapted cultivar, M29519 as recurrent parent, and Edwall, a soft cultivar with good biscuit-making quality, as donor. Segregation ratio's for grain texture were calculated after each backcross. The backcross derivates M29519 (soft) and M29519 (hard) and the donor and recurrent parents were also compared for biscuit-making quality. The microtome method was found to be very effective to determine grain texture. In this study grain softness was determined by a single dominant gene. M29519 (hard) and the recurrent parent did not differ significantly for any quality characteristics. M29519 (hard) and M29519 (soft) differed significantly for seven characteristics associated with biscuit-making quality, and M29519 (soft) produced a significantly larger biscuit diameter than M29519 (hard). M29519 (soft) differed significantly from the donor parent for six of the measured characteristics. Despite this, M29519 (soft) produced a biscuit similar in diameter to that of the donor parent. Therefore, although the transfer of the softness genes into a different genetic background did not transfer all the factors generally associated with good biscuit-making quality, it did produce a biscuit that did not differ significantly from that of the donor.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003908707708
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  • 42
    Digitale Medien
    Digitale Medien
    Resistance to septoria nodorum blotch in the Aegilops tauschii accession RL5271 is controlled by a single gene (2000)
    Springer
    Euphytica 113 (2000), S. 227-231 
    Details
    ISSN: 1573-5060
    Schlagwort(e): disease resistance ; incubation period ; infection frequency ; Stagonospora nodorum ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Septoria nodorum blotch is the most important leaf disease of wheat in Western Australia. A potentially useful source of resistance has been identified in an accession of Aegilops tauschii. To study the genetics of resistance of this source a cross was made between the resistant Ae. tauschii accession, RL5271, and a susceptible accession, CPI110889. The resistant parent took significantly longer to develop symptoms, developed significantly fewer lesions and expressed significantly lower levels of disease than the susceptible parent. The F1 mean response for disease severity indicated there was no complete dominance. The F3 families were classified using three approaches. In the first approach the individual F3 plant response was used to classify the F3 families. In the second approach the F3 family means and standard errors were used to classify the F3 families. In the final approach Best Linear Unbiased Predictors of disease score and standard error for each F3 family derived from a REML analysis were used to classify the F3 families. The genotypic ratios generated by each of the approaches suggested that resistance is controlled by a single gene. The effectiveness of the resistance and its simple genetic control in the Ae. tauschii, accession RL5271 may be a useful resistance source for use in a bread wheat breeding program.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003981525052
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  • 43
    Digitale Medien
    Digitale Medien
    Isolation of mildew resistant wheat-rye translocation lines from a double substitution line (2000)
    Springer
    Euphytica 115 (2000), S. 167-172 
    Details
    ISSN: 1573-5060
    Schlagwort(e): alien genetic variation ; chromosome translocation ; powdery mildew ; resistance ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A powdery mildew resistant double disomic wheat-rye substitution line carrying rye chromosomes 1R and 2R was crossed with normal bread wheats. The F2 generation was analysed cytologically by C-banding. Wheat-rye chromosome translocations involving both rye chromosomes 1R and 2R were frequent in F2. Lines with translocations of 1R and 2R were harvested separately. After four generations of selfing and selection for mildew resistance and fertility, fully fertile resistant lines were selected and analysed cytologically. Lines with 1BL/1RS and 2BS/2RL translocations were identified. The resistance on chromosome 1RS could not be shown to be different from control varieties carrying the same rye segment, while the resistance on 2RL is much broader than the earlier known 2RL derived resistance in the line Transec.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1004018500970
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  • 44
    Digitale Medien
    Digitale Medien
    Accumulation and leakage of abscisic acid during embryo development and seed dormancy in wheat (2000)
    Springer
    Plant growth regulation 30 (2000), S. 253-260 
    Details
    ISSN: 1573-5087
    Schlagwort(e): abscisic acid (ABA) ; dormancy ; mature germination ; seed ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Seed dormancy develops latein embryogenesis after a period of potential prematuregermination and has been associated with levels ofabscisic acid (ABA) in, and sensitivity to, ABA ofembryos. In wheat (Triticum aestivum L.)embryos, there are two peaks in levels of ABA duringdevelopment: the first occurs 25 days afterpollination (DAP) and the second from 35 to 40 DAP. The first peak of ABA appears to be associated withthe development of the embryo's sensitivity to ABAsince such sensitivity was altered in seeds on earsthat were incubated in a solution of ABA from 15 and20 DAP. In the embryos of Kitakei wheat, a line thatexhibits dormancy, the second peak, at around 35 DAP,was more prolonged in comparison to Chihoku, anon-dormant line. The results support the proposedinvolvement of ABA in the formation and maintenance ofseed dormancy during middle and late embryogenesis. When developing embryos were incubated in water,embryonic ABA leaked out from the embryos, inparticular between 30 and 40 DAP. Prematuregermination observed between 30 and 40 DAP might berelated to such leakage of ABA from embryos.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006320614530
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  • 45
    Digitale Medien
    Digitale Medien
    Morphoagronomic and biochemical variation in an Argentinean landrace of wheat (2000)
    Springer
    Genetic resources and crop evolution 47 (2000), S. 281-284 
    Details
    ISSN: 1573-5109
    Schlagwort(e): agronomic traits ; isozymes ; landrace ; Triticum aestivum ; variation ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A sample of an Argentinean landrace of wheat showed considerable variation in most of the evaluated morphological and agronomic characters. However, analyses with high molecular glutenins and two isozyme systems, known to be highly polymorphic among current cultivars, revealed very little or no variation, respectively. The large difference in the observed variation between morphoagronomic and biochemical characters is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008711903949
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  • 46
    Digitale Medien
    Digitale Medien
    Isolation and characterization of the wheat prolyl isomerase FK506-binding protein (FKBP) 73 promoter (2000)
    Springer
    Plant molecular biology 42 (2000), S. 489-497 
    Details
    ISSN: 1573-5028
    Schlagwort(e): ABA-responsive ; FKBP73 ; promoter ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The wheat FK506-binding protein (FKBP) 73 is a member of the peptidyl prolyl cis-trans isomerase gene family, which catalyses the interconversion between the cis and trans forms of the peptide bond preceding proline residues in proteins. A 3.5 kb sequence 5′ upstream of the ATG codon of the wheat FKBP73 was isolated from a wheat genomic library, and characterized by deletion analysis and transient expression in wheat embryos. The 1517 bp fragment is referred to as the full promoter due to the maximal activity of the fused luciferase reporter gene. Sequence analysis revealed the presence of three abscisic acid (ABA)-responsive elements (ABREs) proximal to coupling elements (CE1-like), a putative lectin box, two putative binding sites for the myb transcription factor and a 36 bp fragment which exhibits 100% identity to the pSau3A9 clone located in the centromeric region of wheat chromosomes. In a transient expression assay the promoter preserved the tissue specificity described in vivo, namely it is expressed only in germinating embryos and young shoots. The promoter was induced 1.9-fold by ABA, the minimal promoter was designated at −221 and the TATA box located at −137. The inducibility by ABA and the expression during germination may indicate that FKBP73 belongs to the group of genes induced by ABA upon germination.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006345411056
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  • 47
    Digitale Medien
    Digitale Medien
    Intron-mediated gusA expression in tritordeum and wheat resulting from particle bombardment (2000)
    Springer
    Plant molecular biology 42 (2000), S. 615-622 
    Details
    ISSN: 1573-5028
    Schlagwort(e): introns ; maize ubiquitin promoter ; tritordeum ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The promoterless maize ubiquitin first exon and intron fragment can drive gusA expression in immature tritordeum inflorescences and immature wheat scutella. In fluorescence assays, this fragment induces gusA expression in tritordeum inflorescences to 50 times higher than background. The activity of the complete promoter, exon and intron cassette was up to 20 000-fold higher than background but the maize ubiquitin promoter in isolation had very low activity. A construct with the maize alcohol dehydrogenase first exon and intron had low activity, visible in histochemical assays. Both intron sequences have promoter-like features and in the ubiquitin intron there is a sequence homologous to the opaque-2-binding box. We suggest that the combination of these elements may explain the promoter activity detected in these introns.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006331831858
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  • 48
    Digitale Medien
    Digitale Medien
    A rapid induction by elicitors of the mRNA encoding CCD-1, a 14 kDa Ca2+-binding protein in wheat cultured cells (2000)
    Springer
    Plant molecular biology 42 (2000), S. 807-817 
    Details
    ISSN: 1573-5028
    Schlagwort(e): Ca2+-binding protein ; EF-hand ; elicitor ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Intracellular Ca2+ has been implicated in the signal transduction processes during the development of the plant defense system against fungal pathogens. From wheat cultured cells that had been treated with the elicitor derived from Typhula ishikariensis, the ccd-1 gene encoding a 14 kDa Ca2+-binding protein with an acidic amphiphilic feature was isolated. The ccd-1-encoded protein (CCD-1) shares homology to the C-terminal half domain of centrin, a Ca2+-binding protein conserved in eukaryotes. Unlike typical eukaryotic centrins, CCD-1 contains only one Ca2+-binding loop, which corresponds to the one in the fourth EF-hand from the N-terminus of centrin. The recombinant CCD protein expressed in Escherichia coli bound to a phenyl-Sepharose column in the presence of Ca2+ and was eluted out by EGTA. It also showed a Ca2+-dependent electrophoretic mobility shift on the non-denaturing polyacrylamide gel. The ccd-1 mRNA expression was rapidly induced by treatment with fungal and chitosan oligosaccharide elicitors, implying that it might have a role in transducing Ca2+ signals provoked by the elicitors. The expression of the ccd-1 mRNA was induced by treatment with A23187, and the induction was suppressed by La3+ or 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). This study suggests the involvement of intracellular Ca2+ in the elicitor-induced mRNA expression of a novel class of Ca2+-binding proteins conserved in higher plants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006431724090
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  • 49
    Digitale Medien
    Digitale Medien
    2-Methylisoborneol disposition in three strains of catfish: absence of biotransformation (2000)
    Springer
    Fish physiology and biochemistry 23 (2000), S. 225-232 
    Details
    ISSN: 1573-5168
    Schlagwort(e): methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007834720306
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  • 50
    Digitale Medien
    Digitale Medien
    Neocentric activity of rye 5RL chromosome in wheat (2000)
    Springer
    Chromosome research 8 (2000), S. 543-554 
    Details
    ISSN: 1573-6849
    Schlagwort(e): genomic in-situ hybridization ; meiosis ; neocentromere ; rye ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The neocentric activity of a constriction located on the long arm of rye 5R chromosome (5RL) was analysed. It is not observed in normal rye but it is unusually stretched in bivalents involving 5RL telosomes in wheat–ditelosomic 5RL addition lines. In 20% of metaphase I cells, the 5RL bivalent presents the centromeres oriented to one pole and the constrictions oriented towards the opposite pole with a strong tension. In 5% of the cells, the constriction was able to orient the bivalent to the poles without tension in the centromeres. Sister chromatid cohesion, which is one of the distinct features of centromeric function, is persistent at the constriction in delayed 5RL chromosomes at anaphase I. Neither the elongation of the constriction nor the neocentric activity was observed at second meiotic division or mitosis. FISH studies showed that the 5RL constriction lacked detectable quantities of two repetitive DNA sequences, CCS1 and the 180-bp knob repeat, present at cereal centromeres and neocentromeres, respectively. We propose that, under special conditions, such as the wheat background, the normally non-centromeric DNA present at this region of 5RL acquires a specific chromatin structure, differentiated as an elongated constriction, which is able to function as a centromere.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009275807397
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  • 51
    Digitale Medien
    Digitale Medien
    Distribution and Exudation of Allelochemicals in Wheat Triticum aestivum (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 2141-2154 
    Details
    ISSN: 1573-1561
    Schlagwort(e): Allelopathy ; phenolic acids ; 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one ; DIMBOA ; GC-MS-MS ; wheat ; Triticum aestivum ; weed suppression ; annual ryegrass ; Lolium rigidum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Wheat allelopathy has potential for weed suppression. Allelochemicals were identified in wheat seedlings, and they were exuded from seedlings into agar growth medium. p-Hydroxybenzoic, trans-p-coumaric, cis-p-coumaric, syringic, vanillic, trans-ferulic, and cis-ferulic acids and 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) were identified in both the shoots and roots of 17-day-old wheat seedlings and their associated agar growth medium. Wheat accessions with previously identified allelopathic activity tended to contain higher levels of allelochemicals than poorly allelopathic ones. The allelopathic compounds present in the shoots generally also were identified in the roots and in the agar medium. Allelochemicals were distributed differentially in wheat, with roots normally containing higher levels of allelochemicals than the shoots. When the eight allelochemicals were grouped into benzoic acid and cinnamic acid derivatives, DIMBOA, total coumaric, and total ferulic acids, the amount of each group of allelochemicals was correlated between the roots and the shoots. Most of the allelochemicals identified in the shoots and roots could be exuded by the living roots of wheat seedling into the agar growth medium. However, the amounts of allelochemicals in the agar growth medium were not proportional to those in the roots. Results suggest that wheat plants may retain allelochemicals once synthesized. The presence of allelochemicals in the agar growth medium demonstrated that wheat seedlings were able to synthesize and to exude phytotoxic compounds through their root system that could inhibit the root growth of annual ryegrass.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1005520500110
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  • 52
    Digitale Medien
    Digitale Medien
    Nitrogen in percolation water in paddy fields with a rice/wheat rotation (2000)
    Springer
    Nutrient cycling in agroecosystems 57 (2000), S. 75-82 
    Details
    ISSN: 1573-0867
    Schlagwort(e): nitrogen ; leaching ; paddy soil ; wheat ; rice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Nitrogen in percolation water was observed in paddy field soil under rice/wheat rotation. Different N-application rates were designed. Porous pipes were installed in triplicate at depths of 30, 60 and 90 cm to collect the water in the period of wheat growth. Suction cups were installed in triplicate at the same depths to collect the water during the period of rice growth. NH4 +, NO3 - and total N in the water were analysed with a continuous-flow nitrogen analyzer. Results showed that nitrate was the predominant form of nitrogen in percolation water during the period of wheat growth. Nitrate leaching was high in early spring after the `tillering fertilisation'. More than 50 mg l-1 of nitrate concentration in percolation water was observed for 30 and 60 cm in depth and more than 15 mg l-1 were observed for 90 cm. The concentration decreased quickly and was very low, less than 2 mg l-1 usually, in the earring stage of wheat. Nitrate in water was low, less than 1.5 mg l-1 usually, when the field was flooded during the period of rice growth. Some soluble organic N existed in the water. Nitrate in percolation water increased when the field was drained. The leaching loss of nitrogen during winter wheat growth period was estimated to be about 3.4% of the N-fertiliser applied at the normal application rate of farmers; for the rice growth period it was around 1.8%. Although a reduced N-application decreased N leaching, it caused a marked decrease in crop yield.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009712404335
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  • 53
    Digitale Medien
    Digitale Medien
    Russian wheat aphid-induced protein alterations in spring wheat (2000)
    Springer
    Euphytica 111 (2000), S. 199-203 
    Details
    ISSN: 1573-5060
    Schlagwort(e): Diuraphis noxia (Mordvilko) ; protein ; Russian wheat aphid ; Triticum aestivum ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The Russian wheat aphid (RWA), Diuraphis noxia (Mordvilko), has become a perennial, serious pest of wheat (Triticum aestivum L.) in the western United States. Current methodologies used to enhance RWA resistance in wheat germplasm could benefit from an understanding of the biochemical mechanisms underlying resistance to RWA. This study was initiated to identify specific polypeptides induced by RWA feeding that may be associated with RWA resistance. The effects of RWA feeding on PI 140207 (a RWA-resistant spring wheat) and Pavon (a RWA-susceptible spring wheat) were examined by visualizing, silver-stained denatured leaf proteins separated by two-dimensional polyacrylamide gel electrophoresis. Comparisons of protein profiles of noninfested and RWA-infested Pavon and PI 140207 revealed a 24-kilodalton-protein complex selectively inhibited in Pavon that persisted in PI 140207during RWA attack. No other significant qualitative or quantitative differences were detected in RWA-induced alterations of protein profiles. These results suggest that RWA feeding selectively inhibit synthesis and accumulation of proteins necessary for normal metabolic functions in susceptible plants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003866626723
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  • 54
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Andisol ; phosphatases ; phosphorus ; roots ; VA mycorrhiza ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1004727201568
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  • 55
    Digitale Medien
    Digitale Medien
    Necessity of Superoxide Production for Development of Etiolated Wheat Seedlings (2000)
    Springer
    Biochemistry (Moscow) 65 (2000), S. 1357-1361 
    Details
    ISSN: 1608-3040
    Schlagwort(e): antioxidant ; Endomyces magnusii ; apoptosis ; BHT ; DNA ; fragmentation ; DNA synthesis ; ontogenesis ; ROS ; plant ; protein synthesis ; superoxide ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract It was found that production of superoxide (O2 – ·) is crucial for normal morphogenesis of etiolated wheat seedlings in the early stages of plant development. The development of etiolated wheat seedlings was shown to be accompanied with cyclic changes in the rate of O2 – · production both in the entire intact seedling and in its separated organs (leaf, coleoptile). First increase in the rate of O2 – · production was clearly observed in the period from two to four days of seedling development, then the rate of O2 – · production decreased to the initial level, and then it increased again for two days to a new maximum. An increase in O2 – · production in the period of the first four days of seedling development correlates with an increase in DNA and protein contents in the coleoptile. The second peak of increased rate of O2 – · production observed on the sixth or seventh day of seedling development coincides with a decrease in DNA and protein contents and apoptotic internucleosomal nuclear DNA fragmentation in the coleoptile. Incubation of seedlings in the presence of the antioxidant BHT (ionol) strongly affects their development but it does not influence the increase in DNA and protein contents for the initial four days of seedling life, and it slows down the subsequent age-dependent decrease in protein content and fully prevents the age-dependent decrease in DNA content in the coleoptile. A decrease in the O2 – · amount induced by BHT distorts the seedling development. BHT retards seedling growth, presumably by suppression of cell elongation, and it increases the life span of the coleoptile. It seems that O2 – · controls plant growth by cell elongation at the early stages of seedling development but later O2 – · controls (induces) apoptotic DNA fragmentation and protein disintegration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1002892520658
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  • 56
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): c-Fos ; Dopamine ; D1 ; Hippocampus ; Rat ; Synaptic Plasticity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s10059-000-0546-y
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  • 57
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007597713530
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  • 58
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007605024942
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  • 59
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026418814417
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  • 60
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007552927404
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  • 61
    Digitale Medien
    Digitale Medien
    Mechanism-Based Modeling of Functional Adaptation Upon Chronic Treatment with Midazolam (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 321-327 
    Details
    ISSN: 1573-904X
    Schlagwort(e): benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007505223519
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  • 62
    Digitale Medien
    Digitale Medien
    Relationship between Carbon and Nitrogen Metabolisms in Photosynthesis. The Role of Photooxidation Processes (2000)
    Springer
    Photosynthetica 37 (2000), S. 519-527 
    Details
    ISSN: 1573-9058
    Schlagwort(e): alanine ; aspartate ; glycine ; glycollate ; malate ; nitrate ; serine ; sugars ; Triticum aestivum ; urea ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract 14CO2 uptake in leaves of wheat plants (Triticum aestivum L.) fertilized by urea or Ca(NO3)2 (25 mol m-3) was investigated. The Warburg effect (inhibition of 14CO2 uptake by oxygen) under 0.03 vol. % CO2 concentration was observed only in non-fertilized plants. Under 0.03 vol. % CO2, the Warburg antieffect (stimulation of 14CO2 uptake by oxygen) was detected only in plants fertilized by Ca(NO3)2. Under saturating CO2 concentration (0.30 vol. %), the Warburg antieffect was observed in all variants. Under limitation of ribulose-1,5-bisphosphate carboxylase/oxygenase activity (0.30 vol. % CO2 + 1 vol. % O2), the rate of synthesis of glycollate metabolism products decreased in control and urea-fertilized plants but was enhanced in nitrate-fed plants. Hence, there was an activation of glycollate formation via transketolase reaction in fertilized plants, and the products of nitrate reduction function were oxidants in nitrate-fertilized plants whereas the superoxide radical played this role in urea-fertilized plants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007150921664
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  • 63
    Digitale Medien
    Digitale Medien
    Interactive Effects of Sulphur Dioxide and Mineral Nutrient Supply on Photosynthetic Characteristics and Yield in Four Wheat Cultivars (2000)
    Springer
    Photosynthetica 38 (2000), S. 91-96 
    Details
    ISSN: 1573-9058
    Schlagwort(e): biomass ; carotenoids ; chlorophyll ; nutrients ; sulphur dioxide ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Field experiments were conducted on four cultivars of wheat (Triticum aestivum L.) to examine the variability in cultivar response to sulphur dioxide (SO2) under different concentrations of mineral nutrients. Thirty-days-old plants were exposed for 8 weeks to 390±20 µg m−3 (0.15 ppm) SO2 for 4 h per day, 5 d per week. Decline in net photosynthetic rate, contents of pigments and nitrogen, biomass and grain yield of each cultivars were due to SO2 at all the nutrient concentrations studied. However, the magnitude of reduction was higher in plants grown without nutrient application. On the basis of the reductions in photosynthesis and yield, the susceptibility of wheat cultivars to SO2 was in the order of Malviya 213 〉 Malviya 37 〉 Malviya 206 〉 Malviya 234 at recommended dose of NPK, whereas the same without the nutrients was Malviya 206 〉 Malviya 234 〉 Malviya 213 〉 Malviya 37.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026700109438
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  • 64
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02439270
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  • 65
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Bowel sounds ; Rat ; Motility ; Body acoustics ; Signal detection ; Signal characterisation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02344687
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  • 66
    facet.materialart.
    Unbekannt
    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
    Publikationsdatum: 2000
    Schlagwort(e): Textbook of geophysics ; Textbook of geology ; Textbook of mathematics ; Data analysis / ~ processing ; Modelling ; Inversion
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    BIBLIOGRAFIE SEISMOLOGIE
  • 67
    facet.materialart.
    Unbekannt
    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
    Publikationsdatum: 2000
    Schlagwort(e): 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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    BIBLIOGRAFIE SEISMOLOGIE
  • 68
    Digitale Medien
    Digitale Medien
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Schlagwort(e): variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 69
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007017116171
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  • 70
    Digitale Medien
    Digitale Medien
    Is the inversion effect in rhesus monkeys face-specific? (1999)
    Springer
    Animal cognition 2 (1999), S. 123-129 
    Details
    ISSN: 1435-9456
    Schlagwort(e): Key words Face recognition ; Inversion ; Expertise ¶effect ; Matching-to-sample ;  Macaca mulatta
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s100710050032
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  • 71
    Digitale Medien
    Digitale Medien
    Within-plant distribution of Rhopalosiphum padi on wheat seedlings is affected by induced responses (1999)
    Springer
    Entomologia experimentalis et applicata 93 (1999), S. 227-230 
    Details
    ISSN: 1570-7458
    Schlagwort(e): Rhopalosiphum padi ; cereal aphids ; wheat ; induced responses ; feeding site
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003874225681
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  • 72
    Digitale Medien
    Digitale Medien
    Comparison of Diuraphis noxia resistance in wheat isolines and plant introduction lines (1999)
    Springer
    Entomologia experimentalis et applicata 92 (1999), S. 157-164 
    Details
    ISSN: 1570-7458
    Schlagwort(e): plant resistance ; antibiosis ; tolerance ; antixenosis ; Russian wheat aphid ; wheat ; Homoptera ; Aphididae
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The Russian wheat aphid, Diuraphis noxia (Mordvilko), is one of the most important aphid pests of wheat, Triticum aestivum L., worldwide. Among the various pest management options, plant resistance is an economical management tactic to control D. noxia in cereal crops such as wheat. Researchers have identified D. noxia resistant germplasm and it has been incorporated into wheat. This study compared D. noxia resistance between the ‘Betta’ wheat isolines Betta-Dn1, Betta-Dn2, and Betta-Dn5 and their corresponding donor gene plant introduction (PI) lines PI 137739 (Dn1), PI 262660 (Dn2), and PI 294994 (Dn5). Although the Betta isolines and PI lines showed D. noxia resistance when compared with Betta wheat, the degree of resistance in the isolines to D. noxia was different from their corresponding PI donors. Aphid number, aphid fecundity, and biomass per aphid were not different between Betta-Dn1 and PI 137739 or Betta-Dn2 and PI 262660; however, the same parameters were significantly lower on PI 294994 compared with Betta-Dn5. This indicated that aphid resistance in PI 137739 and PI 262660 was probably governed by a single dominant gene, while the resistance in PI 294994 was controlled by more than one gene. Additionally, plant biomass reduction was aphid density dependent, which suggested that use of appropriate aphid infestation level is important when using plant biomass reduction as an indicator of resistance. Plant resistance categorization showed that there was no detectable difference in antixenosis among the seven lines evaluated. However, the higher aphid fecundity observed on PI 262660 compared with PI 137739 and PI 294994, in addition to no significant differences among the three PIs in plant biomass reduction, suggested PI 262660 was a tolerant line, while PI 137739 and PI 294994 were antibiotic lines. Plant tolerance could not be elucidated among the three Betta isolines using aphid fecundity and plant biomass reduction as indicators.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003719325094
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  • 73
    Digitale Medien
    Digitale Medien
    Salivation into sieve elements in relation to plant chemistry: the case of the aphid Sitobion fragariae and the wheat, Triticum aestivum (1999)
    Springer
    Entomologia experimentalis et applicata 91 (1999), S. 111-114 
    Details
    ISSN: 1570-7458
    Schlagwort(e): sieve element ; salivation ; aphid ; plant resistance ; wheat ; Sitobion fragariae ; Triticum aestivum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Extended sieve element salivation (E1 waveform in the electrical penetration graph) is a characteristic activity during early sieve element punctures, particularly in resistant plants. In order to explore a chemically-mediated mechanism of resistance associated with sieve element salivation, we compared the pattern of feeding behaviour of the aphid, Sitobion fragariae (Walker), on two cultivars of the wheat Triticum aestivum L., with different concentrations of hydroxamic acids (Hx). During 24 h of electronic monitoring, aphids dedicated over 50% of the total time to phloem ingestion from the sieve elements. Total time allocated to E1 in the experiment, time to first E1 within the experiment, time allocated to E1 before a sustained phloem ingestion (E2) and the contribution of sieve element salivation to the phloem phase (E1/[E1+E2]) were significantly higher in the high-Hx cultivar. The increased salivation in plants with higher contents of Hx suggests the existence, at least in this system, of a chemically-mediated sieve element constraint.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1003628703035
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  • 74
    Digitale Medien
    Digitale Medien
    A Modular Vector for Agrobacterium Mediated Transformation of Wheat (1999)
    Springer
    Plant molecular biology reporter 17 (1999), S. 323-331 
    Details
    ISSN: 1572-9818
    Schlagwort(e): Agrobacterium ; modular vector ; transformation ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Wheat (cv Chinese Spring) tissues were transformed using Agrobacterium tumefasciens and a new plasmid modular vector, pMVTBP. We constructed pMVTBP with unique restriction sites connecting (1) the CaMV 35S promoter, (2) a Kozak sequence, (3) the FLAG epitope, (4) the (His)6 epitope, (5) a coding region (for wheat TATA Binding Protein, wTBP) and (6) the CaMV 35S 3′UTR. This vector thus allows easy exchange of different regulatory or coding sequences. Explants of either germinating mature seeds, or immature embryos, were induced to callus for up to two weeks, treated with virulence-induced bacteria for one hour, then regenerated into plantlets. Transient expression of a GUS reporter gene, assayed at about one week, occurred in 10–12% of calluses. Expression of the FLAG-tagged wTBP was also detected, by immunostaining. Stable expression, by selective growth on geneticin, and by GUS expression at about six weeks, occurred in 1–2% of calluses, quite comparable to that achieved by other methods.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1007686408369
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  • 75
    Digitale Medien
    Digitale Medien
    Evaluation of soil extractants for Mn availability and response of wheat to applied Mn in soils of semi-arid zone of Punjab, India (1999)
    Springer
    Nutrient cycling in agroecosystems 53 (1999), S. 139-146 
    Details
    ISSN: 1573-0867
    Schlagwort(e): critical levels of Mn ; soil extractants ; Mn-deficiency ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Seven chemical extractants were tested for their relative performance to predict the response of wheat to Mn application in coarse textured alkaline soils of semi-arid region. Five out of the seven extractants were found to be promising for the estimation of critical level of available Mn in these soils, as the amount of Mn extracted by these extractants was positively and significantly correlated with relative grain yield as well as Mn uptake. The critical deficiency level of soil available Mn with 0.005 M DTPA, 0.02% hydroquinone, 0.02 N sodium pyrophosphate, 0.1N H3PO4 and 0.05N HCl+0.025N H2SO4 was 3.1, 13.8, 23.5, 5.3 and 17.8 mg kg-1 soil, respectively. The 1N ammonium acetate and 0.01M CaCl2 were found to be unsuitable extractants for these soils. Further field trials at eight locations with varying levels of Mn deficiency showed successive increase in the grain yield of wheat with foliar Mn application, emphasizing the need for Mn fertilization when wheat is grown on Mn deficient soils.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009754724227
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  • 76
    Digitale Medien
    Digitale Medien
    Influence of within-field and landscape factors on aphid predator populations in wheat (1999)
    Springer
    Landscape ecology 14 (1999), S. 239-252 
    Details
    ISSN: 1572-9761
    Schlagwort(e): Coccinellidae ; Aphididae ; wheat ; spatial scale ; species diversity ; numerical response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The influence of prey density, within-field vegetation, and the composition and patchiness of the surrounding landscape on the abundance of insect predators of cereal aphids was studied in wheat fields in eastern South Dakota, USA. Cereal aphids, aphid predators, and within-field vegetation were sampled in 104 fields over a three year period (1988–1990). The composition and patchiness of the landscape surrounding each field were determined from high altitude aerial photographs. Five landscape variables, aggregated at three spatial scales ranging from 2.6 km2 to 581 km2, were measured from aerial photographs. Regression models incorporating within-field and landscape variables accounted for 27–49% of the variance in aphid predator abundance in wheat fields. Aphid predator species richness and species diversity were also related to within-field and landscape variables. Some predators were strongly influenced by variability in the composition and patchiness of the landscape surrounding a field at a particular spatial scale while others responded to variability at all scales. Overall, predator abundance, species richness, and species diversity increased with increasing vegetational diversity in wheat fields and with increasing amounts of non-cultivated lands and increasing patchiness in the surrounding landscape.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008002528345
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  • 77
    Digitale Medien
    Digitale Medien
    Management of Stored Wheat Insect Pests in the USA (1999)
    Springer
    Integrated pest management reviews 4 (1999), S. 127-143 
    Details
    ISSN: 1572-9745
    Schlagwort(e): wheat ; stored-grain ; integrated pest management ; aeration ; biological control ; grain sampling ; insect monitoring ; modeling ; area-wide IPM
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Management of stored-grain insect pests by farmers or elevator managers should be based upon a knowledge of the grain storage environment and the ecology of insect pests. Grain storage facilities and practices, geographical location, government policies, and marketing demands for grain quality are discussed as factors influencing stored-grain insect pest management decisions in the United States. Typical practices include a small number of grain samples designed to provide grain quality information for segregation, blending and marketing. This low sampling rate results in subjective evaluation and inconsistent penalties for insect-related quality factors. Information on the efficacy of insect pest management practices in the United States, mainly for farm-stored wheat, is discussed, and stored-grain integrated pest management (IPM) is compared to field-crop IPM. The transition from traditional stored-grain insect pest control to IPM will require greater emphasis on sampling to estimate insect densities, the development of sound economic thresholds and decision-making strategies, more selective use of pesticides, and greater use of nonchemical methods such as aeration. New developments in insect monitoring, predictive computer models, grain cooling by aeration, biological control, and fumigation are reviewed, their potential for improving insect pest management is discussed, and future research needs are examined.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009682410810
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  • 78
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1211
    Schlagwort(e): Key words Class II MHC sequence ; Rat ; Cloning ; RT-PCR ; Polymorphism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002510050676
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  • 79
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Transplantation ; Parkinson’s disease ; CNS fetal development ; CNS differentiation ; Neurotrophic factors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410051285
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  • 80
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Subcommissural organ ; Isograft ; Xenograft ; Reissner’s fiber ; Cerebrospinal fluid ; Rat ; Bovine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410051306
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  • 81
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Axonal transport ; Purkinje cell ; Organotypic culture ; Microinjection ; Antimitotic drugs ; Cytoskeleton ; Dendritic transport ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410051212
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  • 82
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Key words Neurofilament ; Basket cell ; Pinceau ; Golgi apparatus ; Calcium binding protein ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410051246
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  • 83
    Digitale Medien
    Digitale Medien
    Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue (1999)
    Springer
    Cell & tissue research 295 (1999), S. 467-475 
    Details
    ISSN: 1432-0878
    Schlagwort(e): 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
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410051252
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  • 84
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Key words Water channel protein ; Aquaporin ; AQP5 ; Rat ; Salivary glands ; Immunolocalization ; Secretory stimulation ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410051257
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  • 85
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): pharmacokinetics ; capecitabine ; 5-fluorouracil ; phase I trials
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006263400888
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  • 86
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): docetaxel ; plasma assay ; clinical trials ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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®.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1006327302041
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  • 87
    Digitale Medien
    Digitale Medien
    Mapping loci associated with milling yield in wheat (Triticum aestivum L.) (1999)
    Springer
    Molecular breeding 5 (1999), S. 561-568 
    Details
    ISSN: 1572-9788
    Schlagwort(e): wheat ; milling yield ; QTL mapping ; RFLP ; microsatellite
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A partial genetic linkage map constructed using 150 single seed descent (SSD) lines generated from a cross between the hexaploid wheat varieties ‘Schomburgk’ and ‘Yarralinka’ was used to identify loci controlling milling yield. Milling yield data were obtained using seed collected from field trials conducted at different sites over two seasons. The estimated broad-sense heritability of milling yield in this population was calculated as 0.48. In the preliminary analysis, two regions were identified on chromosomes 3A and 7D, which were significantly associated with milling yield and accounted for 22% and 19% of the genetic variation, respectively. Bulked segregant analysis in combination with AFLP identified other markers linked to these loci, as well as an additional region on chromosome 5A, which accounted for 19% of the genetic variation. The applicability of these markers as selection tools for breeding purposes is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009678023431
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  • 88
    Digitale Medien
    Digitale Medien
    Expression of the insecticidal lectin from snowdrop (Galanthus nivalis agglutinin; GNA) in transgenic wheat plants: effects on predation by the grain aphid Sitobion avenae (1999)
    Springer
    Molecular breeding 5 (1999), S. 65-73 
    Details
    ISSN: 1572-9788
    Schlagwort(e): insect resistance ; aphids ; GNA ; lectins ; transgenic plants ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Transgenic wheat plants containing the gene encoding snowdrop lectin (Galanthus nivalis agglutinin; GNA) under the control of constitutive and phloem-specific promoters were generated through the particle bombardment method. Thirty-two independently derived plants were subjected to molecular and biochemical analyses. Transgene integration varied from one to twelve estimated copies per haploid genome, and levels of GNA expression from 0 to ca. 0.2% of total soluble protein were observed in different transgenic plants. Seven transgenic plants were selected for further study. Progeny plants from these parental transformants were selected for transgene expression, and tested for enhanced resistance to the grain aphid (Sitobion avenae) by exposing the plants to nymphal insects under glasshouse conditions. Bioassay results show that transgenic wheat plants from lines expressing GNA at levels greater than ca. 0.04% of total soluble protein decrease the fecundity, but not the survival, of grain aphids. We propose that transgenic approaches using insecticidal genes such as gna in combination with integrated pest management present promising opportunities for the control of damaging wheat pests.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009616413886
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  • 89
    Digitale Medien
    Digitale Medien
    Identification of molecular markers for the detection of the yellow rust resistance gene Yr17 in wheat (1999)
    Springer
    Molecular breeding 5 (1999), S. 167-175 
    Details
    ISSN: 1572-9788
    Schlagwort(e): wheat ; DNA markers ; yellow rust resistance ; Yr17
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The Yr17 gene, which is present in many European wheat cultivars, displays yellow rust resistance at the seedling stage. The gene introduced into chromosome 2A from Aegilops ventricosa was previously found to be closely linked (0.5 cM) to leaf and stem rust resistance genes Lr37 and Sr38, respectively. The objective of this study was to identify molecular markers linked to the Yr17 gene. We screened with RAPD primers, for polymorphism, the DNAs of cv. Thatcher and the leaf rust-resistant near-isogenic line (NIL) RL 6081 of cv. Thatcher carrying the Lr37 gene. Using a F2 progeny of the cross between VPM1 (resistant) and Thésée (susceptible), the RAPD marker OP-Y15580 was found to be closely linked to the Yr17 gene. We converted the OP- Y15580 RAPD marker into a sequence characterized amplified region (SCAR). This SCAR marker (SC-Y15) was linked at 0.8 ± 0.7 cM to the Yr17 resistance gene. We tested the SC-Y15 marker over a survey of 37 wheat cultivars in order to verify its consistency in different genetic backgrounds and to explain the resistance of some cultivars against yellow rust. Moreover, we showed that the Xpsr150-2Mv locus marker of Lr gene described by Bonhomme et al. [6] which possesses A. ventricosa introgression on the 2A chromosome was also closely linked to the Yr17 gene. Both the SCAR SC-Y15 and Xpsr150-2Mv markers should be used in breeding programmes in order to detect the cluster of the three genes Yr17, Lr37 and Sr38 in cross progenies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1009672021411
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  • 90
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): pharmacokinetics ; pharmacodynamics ; effect compartment model ; indirect response ; sigmoid E max ; tiagabine ; GABA uptake inhibitor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1020999114109
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  • 91
    Digitale Medien
    Digitale Medien
    Assuming Peripheral Elimination: Its Impact on the Estimation of Pharmacokinetic Parameters of Muscle Relaxants (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 491-512 
    Details
    ISSN: 1573-8744
    Schlagwort(e): muscle relaxants ; peripheral elimination ; pharmacokinetics ; peripheral concentrations ; volume of distribution ; pharmacokinetic model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract For anesthetic drugs undergoing nonorgan-based elimination, there is a definite trend towards using pharmacokinetic (PK) models in which elimination can occur from both central (k10 ) and peripheral compartments(k20 ). As the latter cannot be assessed directly, assumptions have to be made regarding its value. The primary purpose of this paper is to evaluate the impact of assuming various degrees of peripheral elimination on the estimation of PK parameters. For doing so, an explanatory model is presented where previously published data from our laboratory on three muscle relaxants, i.e., atracurium, doxacurium, and mivacurium, are used for simulations. The mathematical aspects for this explanatory model as well as for two specific applications are detailed. Our simulations show that muscle relaxants having a short elimination half-life are more affected by the presence of peripheral elimination as their distribution phase occupies the major proportion of their total area under the curve. Changes in the exit site dependent PK parameters (Vdss ) are also mostly significant when k20 is smaller than k10 . Although the physiological processes that determine drug distribution and those affecting peripheral elimination are independent, the two are mathematically tied together in the two-compartment model with both central and peripheral elimination. It follows that, as greater importance is given to k20 , the rate of transfer from the central compartment (k12 ) increases. However, as a result of a proportional increase in the volume of the peripheral compartment, peripheral concentrations remain unchanged whether or not peripheral elimination is assumed. These findings point out the limitations of compartmental analysis when peripheral elimination cannot be measured directly.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1023286329945
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  • 92
    Digitale Medien
    Digitale Medien
    The Septoria Tritici and Stagonospora Nodorum Blotch Diseases of Wheat (1999)
    Springer
    European journal of plant pathology 105 (1999), S. 629-641 
    Details
    ISSN: 1573-8469
    Schlagwort(e): wheat ; Triticum spp. ; Septoria tritici ; septoria tritici blotch of wheat Stagonospora nodorum ; stagonospora nodorum blotch of wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008716812259
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  • 93
    Digitale Medien
    Digitale Medien
    Rapid Attainment of Steady-State Plasma Drug Concentrations Within Precise Limits in Multicompartment Mammillary Systems (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 325-328 
    Details
    ISSN: 1573-8744
    Schlagwort(e): anesthetic techniques ; continuous infusion ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract We have previously described a method of rapidly obtaining a specified steady-state plasma concentration of an intravenous drug within precise limits. However the method is limited to drugs whose disposition may be characterized by an open two-compartment system. In this paper, we illustrate how the method can be extended to drugs whose disposition may be characterized by a mammillary model with any number of compartments. Refinements of our previous technique are also described.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1020951230947
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  • 94
    Digitale Medien
    Digitale Medien
    Population Pharmacokinetics and Pharmacodynamics of the Anti-CD11a Antibody hu1124 in Human Subjects with Psoriasis (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 397-420 
    Details
    ISSN: 1573-8744
    Schlagwort(e): psoriasis ; hu1124 ; CD11a ; CD3-positive lymphocytes ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetics of hu1124, a human anti-CD11a antibody, were investigated in human subjects with psoriasis. CD11a is a subunit of LFA-1, a cell surface molecule involved in T cell mediated immune responses. Subjects received a single dose of 0.03, 0.1, 0.3, 0.6, 1, 2, 3, or 10 mg/kg of hu1124 intravenously over 1–3 hr. Blood samples were collected at selected times from 60 min to 72 days after administration. Plasma samples were assayed for hu1124 by ELISA, and pharmacokinetic analyses were performed on the drug plasma concentrations. As the dose of hu1124 was increased, the clearance decreased from 322 ml/day per kg at 0.1 mg/kg to 6.6 ml/day per kg at 10 mg/kg of hu1124. The plasma hu1124 concentration–time profile suggested that the clearance of hu1124 was saturable above 10 μg/ml. In addition, treatment with hu1124 caused a rapid reduction in the level of CD11a expression on CD3-positive lymphocytes (T cells) to about 25% of pretreatment levels. Regardless of the hu1124 dose administered, cell surface CD11a remained at this reduced level as long as hu1124 was detectable (〉0.025 μg/ml) in the plasma. When hu1124 levels fell below 3 μg/ml, the drug was rapidly cleared from the circulation and expression of CD11a returned to normal within 7–10 days thereafter. In vitro, half-maximal binding of hu1124 to lymphocytes was achieved at about 0.1 μg/ml and saturation required more than 10 μg/ml. One of the receptor-mediated pharmacokinetic/pharmacodynamic models which was developed describes the dynamic interaction of hu1124 binding to CD11a, resulting in the removal of hu1124 from the circulation and reduction of cell surface CD11a. The model accounts for the continually changing number of CD11a molecules available for removing hu1124 from the circulation based on prior exposure of cells expressing CD11a to hu1124. In addition, the model also accounts for saturation of CD11a molecules by hu1124 at drug concentrations of approximately 10 μg/ml, thereby reducing the clearance rate of hu1124 with increasing dose.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1020917122093
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  • 95
    Digitale Medien
    Digitale Medien
    Drug–Drug Pharmacodynamic Interaction Detection by a Nonparametric Population Approach. Influence of Design and of Interindividual Variability (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 531-554 
    Details
    ISSN: 1573-8744
    Schlagwort(e): drug–drug interactions ; NPML ; experimental design ; pharmacodynamic variability ; pharmacokinetics ; entropy ; covariate ; second stage model ; controlled trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Population approaches are appealing methods for detecting then assessing drug–drug interactions mainly because they can cope with sparse data and quantify the interindividual pharmacokinetic (PK) and pharmacodynamic (PD) variability. Unfortunately these methods sometime fail to detect interactions expected on biochemical and/or pharmacological basis and the reasons of these false negatives are somewhat unclear. The aim of this paper is firstly to propose a strategy to detect and assess PD drug–drug interactions when performing the analysis with a nonparametric population approach, then to evaluate the influence of some design variates (i.e., number of subjects, individual measurements) and of the PD interindividual variability level on the performances of the suggested strategy. Two interacting drugs A and B are considered, the drug B being supposed to exhibit by itself a pharmacological action of no interest in this work but increasing the A effect. Concentrations of A and B after concomitant administration are simulated as well as the effect under various combinations of design variates and PD variability levels in the context of a controlled trial. Replications of simulated data are then analyzed by the NPML method, the concentration of the drug B being included as a covariate. In a first step, no model relating the latter to each PD parameter is specified and the NPML results are then proceeded graphically, and also by examining the expected reductions of variance and entropy of the estimated PD parameter distribution provided by the covariate. In a further step, a simple second stage model suggested by the graphic approach is introduced, the fixed effect and its associated variance are estimated and a statistical test is then performed to compare this fixed effect to a given value. The performances of our strategy are also compared to those of a non-population-based approach method commonly used for detecting interactions. Our results illustrate the relevance of our strategy in a case where the concentration of one of the two drugs can be included as a covariate and show that an existing interaction can be detected more often than with a usual approach. The prominent role of the interindividual PD variability level and of the two controlled factors is also shown.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1023290530853
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  • 96
    Digitale Medien
    Digitale Medien
    A Compartmental Analysis of the Pharmacokinetics of Propofol in Sheep (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 329-338 
    Details
    ISSN: 1573-8744
    Schlagwort(e): propofol ; anaesthesia ; pharmacokinetics ; compartment models ; effect compartment models
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Conventional compartmental pharmacokinetic analysis may provide inaccurate prediction of drug concentrations after rapid iv administration. To examine this, compartment and effect compartment analysis was applied to measured arterial and brain concentrations of propofol in sheep after iv administration at a range of doses and dose rates. Although arterial and brain concentrations were reasonably well fitted to compartmental and effect compartment models for individual doses and dose rates, the structure and parameters of all models differed with changes in both dose and rate of administration. There were large discrepancies between predicted and measured arterial and brain concentrations when these models were used to predict drug concentrations across doses and dose rates. These data support the limitations of this type of modeling in the setting of rapid propofol administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1020903315017
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  • 97
    Digitale Medien
    Digitale Medien
    Indirect-Response Modeling of Desmopressin at Different Levels of Hydration (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 513-529 
    Details
    ISSN: 1573-8744
    Schlagwort(e): desmopressin ; indirect-response modeling ; overhydration ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The objective of the present study was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmopressin in healthy male subjects at different levels of overhydration. Also, we examined if an indirect-response model could be related to renal physiology and the pharmacological action of desmopressin. Eight healthy male subjects participated in this open, randomized crossover study with three periods. Each subject was orally water loaded (0 to 20ml·kg −1 body weight) on 3 study days in order to achieve three different levels of hydration. After the initial water load, urine was voided every 15 min and the volumes were measured. To ensure continuous overhydration the subjects replaced their fluid loss with drinking-water. When a steady-state diuresis was achieved after approximately 2 hr, 0.396 μg of desmopressin was administered intravenously as a bolus injection. Blood was sampled and urine was collected at intervals throughout the study day (10 hr). An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fit to the urine osmolarity data. There were no statistically significant effects of different levels of hydration, as expressed by urine flow rate at baseline, on the estimates of the PK and PD model parameters. The calculated terminal half-lives of elimination (t1/2 β) ranged between 2.76 and 8.37 hr with an overall mean of 4.36 hr. The overall means of plasma clearance and the volumes of distribution of the central compartment (Vc ) and at steady state (Vss ) were estimated to be 1.34 (SD 0.35) ml·min −1 ·kg −1 , 151 (SD28) ml·kg −1 , and 386 (SD 63) ml·kg −1 , respectively. High urine flow rate, indicating overhydration, produced a diluted urine and thus a low osmolarity at baseline (R0 ). The effect of the urine flow rate on the urine osmolarity at baseline was highly significant (p〈0.0001). The mean values for IC50 and the sigmoidicity factor (γ) were 3.7 (SD 1.2) pg·ml −1 and 13.0 (SD 3.5), respectively. In most cases when there was a high urine flow rate at baseline, the model and the estimated PD parameters could be related to the pharmacological action of desmopressin and renal physiology. Thus, the indirect-response model used in this study offers a mechanistic approach of modeling the effect of desmopressin in overhydrated subjects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1023238514015
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  • 98
    Digitale Medien
    Digitale Medien
    Constructing a Prediction Interval for Time to Reach a Threshold Concentration Based on a Population Pharmacokinetic Analysis: An Application to Basiliximab in Renal Transplantation (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 213-230 
    Details
    ISSN: 1573-8744
    Schlagwort(e): prediction interval ; pharmacokinetics ; population analysis ; NONMEM ; inverse regression ; immunosuppressives
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Basiliximab is an immunosuppressant chimeric monoclonal antibody directed to the human interleukin-2 receptor α-chain used for prevention of acute rejection episodes in organ transplantation. The minimally effective serum concentration necessary to saturate receptor epitopes in kidney transplant patients is 0.2 μg/ml. To guide dose selection for Phase 3 efficacy trials, a population pharmacostatistical model was fitted to intensively sampled Phase 2 pharmacokinetic data. This served as a basis from which to examine candidate dose regimens with respect to the duration over which receptor-saturating concentrations would be achieved posttransplant. Three prediction methods were assessed: one based on simulations, and two others based on first-order approximation using either inverse regression or inversion of confidence intervals. An 80% prediction interval was generated by each method to evaluate its predictive performance against prospectively collected Phase 3 data in 39 renal transplant patients who received two injections of 20mg basiliximab, one prior to surgery and one on Day 4 posttransplant. All methods provided correct prediction of the duration of receptor-saturating concentration. As anticipated, the best performance was obtained from the simulation method which predicted 30 values in the 80% prediction interval, 19.7–52.7 days. The actually observed 80% interval from the Phase 3 data was 23.7–58.3 days.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1020658023774
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  • 99
    Digitale Medien
    Digitale Medien
    Modeling Interactions between Adrenal Suppression and T-Helper Lymphocyte Trafficking during Multiple Dosing of Methylprednisolone (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 559-575 
    Details
    ISSN: 1573-8744
    Schlagwort(e): T-helper cells ; trafficking ; rebound ; corticosteroids ; circadian rhythm ; methylprednisolone ; drug interactions ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A physiologic pharmacodynamic model was developed to jointly characterize the effects of corticosteroid treatment on adrenal suppression and T-helper cell trafficking during single and multiple dosing in asthmatic patients. Methylprednisolone (MP), cortisol, and T-helper cell concentrations obtained from a previously published study during single day and 6 days of multiple dosing MP treatment were examined. The formation and disposition kinetics of MP were described with a compartmental model. The biorhythmic profile of basal cortisol secretion rate was analyzed using a recent Fourier approach based on circadian harmonics. A three-compartment loop model was proposed to represent three major T-helper cell pools: blood, extravascular site, and lymph nodes. T-helper cell synthesis and degradation rate constants were obtained from the literature. The suppressive effects of cortisol and MP on T-helper cell concentrations were described with a joint additive inhibition function altering the cell migration rate from lymph nodes to blood. The model adequately described both plasma cortisol profiles and T-helper cells in blood after single and multiple doses of MP. The potency of MP for suppression of cortisol secretion was estimated as IC50 = 0.8 ng/ml. The biorhythmic nature of the basal T-helper cells in blood was well described as under the influence of basal circadian cortisol concentrations with IC50 = 79 ng/ml. The model fitted potency of MP for suppression of T-helper cells was IC50 = 4.6 ng/ml. The observed rebound of T-helper cells in blood can also be described by the proposed model. The rhythm and suppression of plasma cortisol and T-helper cells before and during single and multiple dose MP treatment were adequately described by these extended indirect response models.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1020974408657
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  • 100
    Digitale Medien
    Digitale Medien
    Relationship Between Etomidate Plasma Concentration and EEG Effect in the Rat (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 924-929 
    Details
    ISSN: 1573-904X
    Schlagwort(e): etomidate ; pharmacokinetics ; pharmacodynamics ; rat ; electroencephalogram
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The effect-plasma concentration relationship of etomidate was studied in the rat using electroencephalographic changes as a pharmacodynamic parameter. Methods. Etomidate was infused (50 mg/kg/h) in chronically instrumented rats (n = 6) until isoelectric periods of 5 s or longer were observed in the electroencephalogram (EEG). The EEG was continuously recorded during the experiment and frequent arterial blood samples were taken for determination of etomidate plasma concentrations. The changes observed in the raw EEG signal were quantified using aperiodic analysis in the 2.5−7.5 Hz frequency band. The return of the righting reflex was used as another parameter of anesthesia. Results. A mean dose of 8.58 ± 0.41 mg/kg needed to be infused to reach the end point of 5 s isoelectric EEG. The plasma concentration time profiles were most adequately fitted using a three-exponential model. Systemic clearance, volume of distribution at steady-state and elimination half-life averaged 93 ± 6 ml/min/kg, 4.03 ± 0.24 l/kg and 59.4 ± 10.7 min respectively. The EEG effect-plasma concentration relationship was biphasic exhibiting profound hysteresis. Semi-parametric minimization of this hysteresis revealed an equilibration half-life of 2.65 ± 0.15 min, and the biphasic effect-concentration relationship was characterized nonparametrically by descriptors. The effect-site concentration at the return of the righting reflex was 0.44 ± 0.03 μg/ml. Conclusions. The results of the present study show that the concentration-effect relationship of etomidate can be characterized in individual rats using aperiodic analysis in the 2.5−7.5 Hz frequency band of the EEG. This characterization can be very useful for studying the influence of diseases on the pharmacodynamics of etomidate in vivo.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1018894523734
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