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  • pharmacokinetics  (2,025)
  • nitrogen  (794)
  • Springer  (2,819)
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  • 1
    ISSN: 1573-8221
    Keywords: acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.
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  • 2
    ISSN: 1573-8264
    Keywords: alfalfa ; arbuscular mycorrhizal fungi ; nitrogen ; nitrogen-fixing bacteria ; phosphorus ; plant growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The aim of this research was to carry out a critical study of the method of obtaining size equivalence between non-symbiotic alfalfa and alfalfa associated with Glomus and/or Rhizobium by applying fixed addition rates of nutrients to the non-symbiotic controls. The experimental design included three nutrient response curves in which the levels of added phosphorus and/or nitrogen were constant during the whole plant growth process: 1) a phosphorus response curve, in order to compare the growth of double symbiotic plants with that of only-Rhizobium inoculated ones; 2) a nitrogen response curve, that consisted of a comparison between the growth of double symbiotic alfalfa and four treatments associated only with Glomus; 3) a phosphorus and nitrogen response curve, to compare the growth of non-inoculated alfalfa with that of double symbiotic plants. Although similar size was achieved among some treatments at harvest, shoot growth over time and nutrient concentrations in tissues differed, indicating that growth equivalence did not mean functional equivalence. A second experimental design was performed taking into account the establishment of microsymbionts for determining the adequate moment to add supplemental phosphorus and/or nitrogen. It included four treatments: a) double symbiotic plants (MR); b) plants inoculated with Rhizobium only (R); c) plants inoculated with Glomus only (M), and d) non-inoculated plants (N). Great similarity in terms of plant growth and nutrient contents in tissues were obtained. Moreover, symbiotic plants were able to produce similar dry matter than non-symbiotic ones under P and N limitations.
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  • 3
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    Electronic Resource
    Springer
    Biologia plantarum 43 (2000), S. 611-613 
    ISSN: 1573-8264
    Keywords: carbon ; hydrogen ; nitrogen ; reducing sugars ; starch ; summer and winter temperature regime
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Two-year-old plants of Karwinskia humboldtiana Zucc. and Karwinskia parvifolia Rose grown from the seeds in greenhouse were transferred to the growth cabinet and cultivated for two months under different temperature regimes (35/20 °C - the summer temperature regime, SR, and 20/5 °C - the winter temperature regime, WR). These temperatures were similar to the temperature conditions in the natural areas of the species studied (Nuevo León, Mexico). The root respiration rate was higher in the plants cultivated under SR than in those under WR. Roots of K. parvifolia res faster in both temperature regimes than roots of K. humboldtiana. Starch content in roots was higher in the plan cultivated under SR, however, concentrations of the other investigated organic and inorganic compounds were higher in the plants cultivated under WR. In K. humboldtiana roots, higher concentration of reducing sugars, carbon and hydrogen were found than in K. parvifolia.
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  • 4
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    Pharmaceutical research 17 (2000), S. 1426-1431 
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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  • 5
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
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  • 6
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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  • 7
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
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  • 8
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    Pharmaceutical research 17 (2000), S. 127-134 
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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  • 9
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
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  • 10
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    Pharmaceutical research 17 (2000), S. 903-905 
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 11
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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  • 12
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
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  • 13
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
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  • 14
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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  • 15
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
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  • 16
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
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  • 17
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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  • 18
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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  • 19
    ISSN: 1573-143X
    Keywords: nitrogen ; organic matter ; shrimp culture ; sulphur cycle bacteria ; water quality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 20
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    Nutrient cycling in agroecosystems 56 (2000), S. 79-85 
    ISSN: 1573-0867
    Keywords: exchangeable cations ; nitrogen ; soil carbon ; soil quality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The long term impact of excreta return on some chemical and biological properties of a pasture soil fertilised with sulphur and phosphate was studied in a system that had been with or without excreta for 23 years. Excreta free areas that had developed under electric fencelines, and parallel transects in the paddocks, were sampled to provide this comparison. Sampling was to 300 mm depth in 0–75, 75–150 and 150–300 mm sections. Total carbon and nitrogen were 20% higher in the 0–150 mm soil layer of areas receiving excreta but did not differ in the 150–300 mm layer. Carbon:nitrogen ratios were similar in both systems as was mineralisable nitrogen, both absolutely and as a percentage of total in the 0–75 mm layer. Significantly more N was mineralised in the 75–150 mm layers of the areas receiving excreta but this was reversed in the 150–300 mm layer. Nitrification rate was higher in all layers of the excreta areas. Inorganic and organic P fractions did not differ significantly. Total P was significantly higher in the 0–75 mm layer and significantly lower in the 150–300 mm layer of the excreta areas. Exchangeable potassium was much higher throughout the excreta areas while this was offset by calcium. The sum of the cations was similar in both areas. Excreta affected most of the diagnostic soil tests used for fertiliser recommendations. The soil properties measured did not reflect clearly the differences in productivity that were obvious in the two areas. It is concluded that excreta return has a impact resulting in increased organic matter storage. Short-term effects of urine have a greater impact on productivity. The major effect is on the disposition of cations and available P.
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  • 21
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    Nutrient cycling in agroecosystems 56 (2000), S. 139-152 
    ISSN: 1573-0867
    Keywords: nitrogen ; N leaching ; liquid manure ; catch crops ; N mineralization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Results are presented from five years (1990–1995) of a field leaching experiment on a sandy soil in south-west Sweden. The aim was to study N leaching, change in soil organic N and N mineralization in cropping systems with continuous use of liquid manure (two application rates) and catch crops. N leaching from drains, N uptake in crops and mineral N in the soil were measured. Simulation models were used to calculate the N budget and N mineralization in the soil and to make predictions of improved fertilization strategies in relation to manure applications and changing the time for incorporation of catch crops. In treatments without catch crops, a normal and a double application of manure increased average N leaching by 15 and 34%, respectively, compared to treatment with commercial fertilizer. Catch crops reduced N leaching by, on average, 60% in treatments with a normal application of manure and commercial fertilizer, but only by 35% in the treatment with double the normal application rate of manure. Incorporation of catch crops in spring increased simulated net N mineralization during the crop vegetation period, and also during early autumn. In conclusion, manured systems resulted in larger N leaching than those receiving commercial fertilizer, mainly due to larger applications of mineral N in spring. More careful adaptation of commercial N fertilization with respect to the amounts of NH4-N applied with manure could, according to the simulations, reduce N leaching. Under-sown ryegrass catch crops effectively reduced N leaching in manured systems. Incorporating catch crop residues in late autumn instead of spring might be preferable with respect to N availability in the soil for the next crop, and would not increase N leaching.
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  • 22
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    Nutrient cycling in agroecosystems 56 (2000), S. 231-240 
    ISSN: 1573-0867
    Keywords: nitrogen ; N ; nitrate ; ammonia ; dairy farming ; systems research ; environment ; sandy soils ; groundwater ; leaching
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In the sandy regions of The Netherlands, high losses of N from intensified dairy farms are threatening the environment. Therefore, government defined decreasing maximum levy-free N surplusses for the period 1998–2008. On most dairy farms, the current N surplus has to be reduced by half at least. Farmers fear that realizing these surplusses will be expensive, because it limits application of animal manure, which then has to be exported or additional land has to be bought. Moreover, farmers are worried about the impact on soil fertility. To explore the possibilities for reducing surplusses of average intensive farms by improved nutrient management, farming systems research is carried out at prototype farm ‘De Marke’. Results are compared with results of a commercial farm in the mid-1980s, the moment that systems research started and introduction of the milk quota system put a halt to further intensification. Results indicate that average intensive farms can realise a reduction in N surplus to a level below the defined final maximum, without the need to buy land or to export slurry. Inputs of N in purchased feeds and fertilisers decreased by 56 and 78%, respectively. Important factors are reduced feed intake per unit milk, as a result of a higher milk yield per cow, less young stock and judicious feeding, an improved utilization of ‘home-made’ manure and a considered balance between the grassland and maize area. Changed soil fertility status did not constrain crop production. Nitrate concentration in the upper groundwater decreased from 200 to 50 mg l-1, within a few years.
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  • 23
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    Nutrient cycling in agroecosystems 57 (2000), S. 75-82 
    ISSN: 1573-0867
    Keywords: nitrogen ; leaching ; paddy soil ; wheat ; rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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.
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  • 24
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    Nutrient cycling in agroecosystems 57 (2000), S. 13-22 
    ISSN: 1573-0867
    Keywords: biogeochemistry ; estuary ; nitrogen ; river ; transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Long-term results of the monthly measurement of dissolved inorganic nitrogen (DIN) concentrations in three major rivers in China are presented. These data are combined with river discharge data to calculate the DIN loads discharged into the ocean. About 774.90 × 103, 55.38 × 103and 144.55 × 103tons of DIN were transported to their respective estuaries each year by the Changjiang, the Huanghe and the Zhujiang in 1980–1989, mainly in the form of nitrate (〉 80 percent). The annual transport of DIN and mean concentration of nitrate in the Changjiang had increased drastically (four-fold) in the last 29 years, especially during the 1980s. Although nitrate concentrations of the Zhujiang and the Huanghe had also increased in the 1980s, their total annual loads of DIN varied mainly with annual runoff volumes, showing no obvious uptrends. Our results also demonstrate that the majority of the DIN load of each river was transported in the high-flow period (70–80 percent). A positive relationship is observed between the annual DIN transport of the Changjiang and the annual application of chemical fertilizers in its catchment. The annual DIN loads of the Huanghe and the Zhujiang were influenced mainly by runoff volume, and also by application of chemical fertilizers.
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  • 25
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    Nutrient cycling in agroecosystems 57 (2000), S. 1-12 
    ISSN: 1573-0867
    Keywords: Asia ; fertilizer ; ammonia ; food ; greenhouse effect ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The addition of anthropogenic N by food and energy production to the global environment contributes to the greenhouse effect, acid deposition, photochemical smog, stratospheric ozone depletion and eutrophication of fresh and marine waters. On a global basis, anthropogenic N mobilization is greater then natural sources of bio-reactive N. Currently, Asia is a hotspot of N mobilization and distribution to downwind and downstream environments, primarily due to food production. Asia's contribution will continue to increase, not only due to population growth, but also to increases in the per capita consumption of food and energy. This paper provides an overview of the global N cycle, presents an analysis of N dynamics within agroecosystems, examines N mobilization in Asia and discusses possible rates of N mobilization in the future.
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  • 26
    ISSN: 1570-7458
    Keywords: EPG ; stylectomy ; phloem amino acids ; nitrogen ; aphid-plant interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Effects of nitrogen deficiency in hydroponically grown barley seedlings (Hordeum vulgare L.) on the development and reproduction of the aphid Rhopalosiphum padi (L.) (Hemiptera: Aphididae) were investigated. Plant growth was significantly reduced in seedlings grown without nitrogen. Aphid intrinsic rate of increase (r m) was also significantly lower on these plants compared with that on plants grown with 8 mol m−3 nitrogen. Phloem sap was collected from seedling stems by aphid stylectomy and amino acids quantified by HPLC. There was a significant reduction in the concentration of non-essential amino acids as a group, but not of essential amino acids. Electrical penetration graphs (EPG) indicated that aphids reached the phloem more quickly and fed for longer on plants grown with nitrogen. This is the first reported study in which this combination of techniques has been used to understand the interactions of an aphid and plant under different environmental conditions.
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  • 27
    ISSN: 1573-5117
    Keywords: nutrient flux ; nitrogen ; phosphate ; tidal flats ; temperature ; geographical comparison
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract During an annual cycle, flux rates of oxygen, nitrate, nitrite, ammonium, phosphate and silicate were measured in light and dark bell jars at three sites in Ria Formosa (Algarve, Portugal) enclosing either a natural macrophytic community (macroalgae on sand or mud, a seagrass bed of Zostera noltii) or bare sediments. The results are compared with a preceeding study in which the same bell jar technique has been applied in the Sylt-Rømø Bay of the northern Wadden Sea. Nitrate flux was mainly directed from the water column to the benthic communities in Ria Formosa, as well as in the Sylt-Rømø Bay. However, nitrate uptake was higher in the northern, more eutrophic study area. In Ria Formosa, nutrient concentrations were lower than in the Sylt-Rømø Bay possibly due to strong water exchange with Atlantic waters. High temperatures and strong insolation had a greater impact on nitrate fluxes in Ria Formosa than in the Sylt-Rømø Bay. Bioturbating macrofauna increased ammonium efflux in the Sylt- Rømø Bay while this effect was not as pronounced in the Ria Formosa study sites. Benthic phosphate uptake dominated in the Ria Formosa and was correlated to initial phosphate concentrations in incoming waters. At both study sites, oxygen and nutrient fluxes were correlated with temperature. Additionally, flux rates were strongly influenced by biotic components and levels of eutrophication. A literature survey showed that mainly in temperate regions, material fluxes increase with temperature, whereas in warmer areas, ammonium and phosphate fluxes between sediment and water were generally lower.
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  • 28
    ISSN: 1573-515X
    Keywords: acid deposition ; atmospheric deposition ; nitrate ; nitrification ; nitrogen ; soil carbon ; soil chemistry ; stream water acidification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Cumulative effects of atmospheric N deposition mayincrease N export from watersheds and contribute tothe acidification of surface waters, but naturalfactors (such as forest productivity and soildrainage) that affect forest N cycling can alsocontrol watershed N export. To identify factors thatare related to stream-water export of N, elevationalgradients in atmospheric deposition and naturalprocesses were evaluated in a steep, first-orderwatershed in the Catskill Mountains of New York, from1991 to 1994. Atmospheric deposition of SO 4 2− , andprobably N, increased with increasing elevation withinthis watershed. Stream-water concentrations ofSO 4 2− increased with increasing elevationthroughout the year, whereas stream-waterconcentrations of NO 3 − decreased withincreasing elevation during the winter and springsnowmelt period, and showed no relation with elevationduring the growing season or the fall. Annual exportof N in stream water for the overall watershed equaled12% to 17% of the total atmospheric input on thebasis of two methods of estimation. This percentagedecreased with increasing elevation, from about 25%in the lowest subwatershed to 7% in the highestsubwatershed; a probable result of an upslope increasein the thickness of the surface organic horizon,attributable to an elevational gradient in temperaturethat slows decomposition rates at upper elevations. Balsam fir stands, more prevalent at upper elevationsthan lower elevations, may also affect the gradient ofsubwatershed N export by altering nitrification ratesin the soil. Variations in climate and vegetationmust be considered to determine how future trends inatmospheric deposition will effect watershed export ofnitrogen.
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  • 29
    ISSN: 1573-515X
    Keywords: Bouteloua eriopoda ; Chihuahuan Desert ; desertification ; hydrology ; Larrea tridentata ; nitrogen ; nutrient budgets ; phosphorus ; runoff
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Losses of dissolved nutrients (N, P, K, Ca, Mg, Na,Cl, and SO4) in runoff were measured on grasslandand shrubland plots in the Chihuahuan desert ofsouthern New Mexico. Runoff began at a lowerthreshold of rainfall in shrublands than ingrasslands, and the runoff coefficient averaged 18.6%in shrubland plots over a 7-year period. In contrast,grassland plots lost 5.0 to 6.3% of incidentprecipitation in runoff during a 5.5-year period. Nutrient losses from shrubland plots were greater thanfrom grassland plots, with nitrogen losses averaging0.33 kg ha−1 yr−1 vs0.15 kg ha−1 yr−1, respectively, during a 3-year period. Thegreater nutrient losses in shrublands were due tohigher runoff, rather than higher nutrientconcentrations in runoff. In spite of these nutrientlosses in runoff, all plots showed net accumulationsof most elements due to inputs from atmosphericdeposition. Therefore, loss of soil nutrients byhillslope runoff cannot, by itself, account for thedepletion of soil fertility associated withdesertification in the Chihuahuan desert.
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  • 30
    ISSN: 1573-515X
    Keywords: chloride ; internal eutrophication ; nitrogen ; peat soil ; phosphorus ; phytometer ; sulphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Inputs of surface waters high in chloride and sulphateincreased the availability of nutrients in fenpeatlands. This `internal eutrophication' wasdemonstrated with test plants (`phytometers') andthrough water and soil analysis. Three experiments arepresented in which the level of chloride and/orsulphate was increased to 3 mmolc l−1. Inexperiment 1 chloride levels were increased from 0.5to 3 mmolc l−1 as CaCl2 or NaCl. Inexperiment 2 and 3 similar increased levels forchloride and sulphate (3 mmolc l−1; as NaCland Na2SO4) were used. The following resultswere found: (i) No differences in soil total-N and total-P werefound before and after the treatments in any of thethree experiments. (ii) Experiment 1 showed a significant increase inBio-Available P (BAP) in pots planted with Anthoxanthum odoratum as well as in bare pots for theNaCl and CaCl2 treatments. The plants in thesetreatments had taken up much more P. (iii) Experiment 2 showed an increase in soil BAPafter treatment with chloride and sulphate in potsplanted with Anthoxanthum odoratum. The chloridetreatment had no effect on plant biomass, whereas thesulphate treatment resulted in a reduction in rootbiomass and root N and P content. The shoots showedan increase in P content in the sulphate and chloridetreatments, while N content remained the same. (iv) In experiment 3, treatments with chloride andsulphate led to significantly increased biomass and Puptake of Anthoxanthum odoratum. Again, noeffects on N uptake were found. These experiments provide evidence for distinctlyincreased availability of phosphate in peat soils whenthese come into contact with water with evenmoderately increased sulphate or chloride levels.Surface water originating from the Rhine river, whichis enriched in chloride and sulphate, is oftensupplied to fen reserves in The Netherlands, tocompensate for water losses due to agriculturaldrainage in the region. The results of this study showthat phosphate availability to the vegetation may risedrastically, with detrimental effects on the speciesdensity and the occurrence of rare species in thevegetation. Hence, supply of this water should beavoided.
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  • 31
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    Hydrobiologia 432 (2000), S. 101-111 
    ISSN: 1573-5117
    Keywords: Hawaii ; light ; nitrogen ; nutrients ; periphyton ; phosphorus ; spate ; stream
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To date, most studies of light- and nutrient-limited primary productivity in forested streams have been carried out in deciduous forests of temperate, continental regions. Conceptual models of light and nutrient limitation have been developed from these studies, but their restricted geographic range reduces the generality of such models. Unlike temperate continental streams, streams on tropical high islands are characterized by flashy, unpredictable discharge and riparian canopies that do not vary seasonally. These contrasting conditions suggest that patterns of light and nutrient limitation in tropical streams may differ from those in temperate streams. The effects of light, and nitrogen and phosphorus availability on periphyton accrual (measured as chlorophyll a per unit area) were investigated using field experiments in 4 low-order streams on the island of Oahu, Hawaii. Levels of chlorophyll a in partially-shaded stream pools were significantly greater than in heavily-shaded pools, and nutrient-enrichment increased the level of chlorophyll a in partially-shaded pools but not in heavily-shaded pools. In each stream, phosphate enrichment resulted in an increase in the level of chlorophyll a, but nitrate enrichment had no effect. Spates following rainstorms occur frequently in these streams, and may increase periphyton productivity by increasing the flux of nutrients to algal cells. However, differences in inorganic nitrogen and phosphorus concentrations measured during spates and baseflow were small, and during some spates, concentrations of these two nutrients declined relative to baseflow concentrations. These observations suggest that phosphorus limitation was not alleviated by spates.
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  • 32
    ISSN: 1573-515X
    Keywords: carbon ; landscape geochemical flows ; model ; nitrogen ; phosphorus ; wetland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract The importance of landscape geochemical flows wasinvestigated using a dynamic model simulating carbon,nitrogen and phosphorus cycling in riverine wetlands,which has been described in a previous paper. Thehydro-geomorphic unit (HGMU) concept was incorporatedin the model by defining a separate, completeunit-model for each unit (HGMU) within the wetland.These unit-models were connected by defining the flowsof nitrogen and phosphorus between them. These flows,also called landscape geochemical flows, usuallyconsist of flows of water containing N and P. The model was applied to a site at Kismeldon Meadows,in south-western England. This site consists of twounits, a slope and a floodplain, separated by a ditch,which catches most of the run off and shallowgroundwater flows from the slope. Only an estimated1% of the N and P that leaves the slope unit in thewater outflow reaches the floodplain unit; the rest iscaught in the system of ditches, which prevent thegeochemical flows taking their natural course. Toexamine the influence of this system of ditches, themodel was run for the same site, but without theditches. This is comparable to a situation of arestored site, where run off and shallow groundwaterflows containing nutrients, can freely get from theslope to the floodplain. The computer simulation experiment reconnecting theslope and floodplain showed that this (1) increasedthe nutrient input into the floodplain, causing ahigher biomass production, and (2) increased thewetness of the floodplain, causing slowerdecomposition, which together (3) led to a faster soilorganic matter accumulation in the floodplain.Nutrient inflows became relatively more importantcompared to atmospheric deposition, especially forphosphorus. By connecting the slope and the floodplainmore nitrogen and less phosphorus flowed into theriver.
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  • 33
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    Fish physiology and biochemistry 23 (2000), S. 225-232 
    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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  • 34
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    Hydrobiologia 426 (2000), S. 185-192 
    ISSN: 1573-5117
    Keywords: nutrient competition ; periphyton ; nitrogen ; silicate ; eutrophication ; benthic microalgae ; hard substrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In order to understand the effect of changing nutrient conditions on benthic microalgae on hard substrates, in-situ experiments with artificial substrates were conducted in Kiel Fjord, Western Baltic Sea. As an extension of previous investigations, we used artificial substrates without silicate and thus were able to supply nutrient media with different Si:N ratios to porous substrates, from where they trickled out continuously. The biofilm developing on these substrates showed a significant increase in biovolume due to N + P enrichment, while Si alone had only minor effects. The stoichiometric composition of the biomass indicated nitrogen limitation during most of the year. The C:N ratios were lowered by the N + P addition. The algae were dominated by diatoms in most cases, but rhodophytes and chlorophytes also became important. The nutrient treatment affected the taxonomic composition mostly at the species level. The significance of the results with regard to coastal eutrophication is discussed.
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  • 35
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    Journal of aquatic ecosystem stress and recovery 8 (2000), S. 53-66 
    ISSN: 1573-5141
    Keywords: Canada ; nitrogen ; periphyton ; phosphorus ; pulp mill effluent ; rivers ; sewage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To evaluate the effects of pulp mill and municipal sewageeffluents on the nitrogen (N) and phosphorus (P) status of northernCanadian rivers, the Northern River Basins Study required an integratedresearch and assessment program consisting of field observation andexperimentation. Analysis of monitoring data collected over 3–13 yshowed that on an annual basis, pulp mills contributed 22% of theP and 20% of the N load discharged from the Wapiti to the Smokyriver, and 6 to 16% of the P load and 4 to 10% of the Nload in the Athabasca River. Despite these low contributions, N and Pconcentrations were elevated below pulp mill discharges on all threerivers during the low discharge period of September to April. Insitu experiments conducted with nutrient diffusing substrata showedthat periphyton biomass was maintained at low levels by insufficient Pin the upper reaches of the Athabasca River and insufficient N+P inthe Wapiti River upstream of point-source discharges. In contrast,effluent loading from pulp mill and sewage inputs alleviated nutrientlimitation downstream of major discharges on both rivers. Experimentsconducted in artificial streams located beside the Athabasca Riverupstream of the first pulp mill showed that P addition increasedperiphyton biomass (expressed as chlorophyll a content) suchthat biomass increased sharply at low P concentrations (2–5µg/L soluble reactive P) and approached saturation at 35µg/L soluble reactive P. As a result of recommendations fromthis integrated program of river monitoring and experimentation,nutrient loading has been reduced to the most affected river(Wapiti-Smoky) and federal and provincial departments of environment arereviewing loading limits for other river reaches.
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  • 36
    ISSN: 1573-5117
    Keywords: Ascophyllum ; Fucus ; CNBM ; light ; nitrogen ; phlorotannins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phlorotannins, C-based defence compounds in brown seaweeds, show a high degree of spatial and temporal variation within seaweed species. One important model explaining this variation is the Carbon Nutrient Balance Model (CNBM), which states that the relative supply of carbon and limiting nutrients will determine the level of defence compounds in plants. Nitrogen is often considered to be the limiting nutrient for marine macroalgal growth and the CNBM thus predicts that when the carbon:nitrogen ratio is high, photosynthetically fixed carbon will be allocated to production of phlorotannins. In the present study, we evaluated the effects of light (i.e. carbon) and nitrogen on the phlorotannin content of two intertidal brown seaweeds, Ascophyllum nodosum and Fucus vesiculosus. This was done in an observational field study, as well as in a manipulative experiment where plants from habitats with different light regimes were subjected to different nitrogen and light treatments, and their phlorotannin content was measured after 14 days. The results showed that there was a negative relationship between tissue nitrogen and phlorotannin content in natural populations of F. vesiculosus, but not in A. nodosum. In the short term, the phlorotannin content in both algal species was not affected by changes in nitrogen availability. Exposure to sunlight had a positive effect on the phlorotannin content in natural populations of both algal species but, in the manipulative experiment, only F. vesiculosus showed a rapid response to changes in light intensities. Plants subjected to sunlight contained higher phlorotannin content than shaded plants. In conclusion, the results imply that nitrogen availability explains some of the natural variation in the phlorotannin content of F. vesiculosus, but the light environment has greater importance than nitrogen availability in predicting the phlorotannin content of each species.
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  • 37
    ISSN: 1573-515X
    Keywords: C:N ratio ; dissolved organic carbon ; dissolved organic nitrogen ; nitrogen ; stream chemistry ; watershed
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Relatively high deposition ofnitrogen (N) in the northeastern United States hascaused concern because sites could become N saturated.In the past, mass-balance studies have been used tomonitor the N status of sites and to investigate theimpact of increased N deposition. Typically, theseefforts have focused on dissolved inorganic forms ofN (DIN = NH4-N + NO3-N) and have largelyignored dissolved organic nitrogen (DON) due todifficulties in its analysis. Recent advances in themeasurement of total dissolved nitrogen (TDN) havefacilitated measurement of DON as the residual of TDN− DIN. We calculated DON and DIN budgets using data onprecipitation and streamwater chemistry collected from9 forested watersheds at 4 sites in New England. TDNin precipitation was composed primarily of DIN. Netretention of TDN ranged from 62 to 89% (4.7 to 10 kghaminus 1 yrminus 1) of annual inputs. DON made up themajority of TDN in stream exports, suggesting thatinclusion of DON is critical to assessing N dynamicseven in areas with large anthropogenic inputs of DIN.Despite the dominance of DON in streamwater,precipitation inputs of DON were approximately equalto outputs. DON concentrations in streamwater did notappear significantly influenced by seasonal biologicalcontrols, but did increase with discharge on somewatersheds. Streamwater NO3-N was the onlyfraction of N that exhibited a seasonal pattern, withconcentrations increasing during the winter months andpeaking during snowmelt runoff. Concentrations ofNO3-N varied considerably among watersheds andare related to DOC:DON ratios in streamwater. AnnualDIN exports were negatively correlated withstreamwater DOC:DON ratios, indicating that theseratios might be a useful index of N status of uplandforests.
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  • 38
    ISSN: 1573-5117
    Keywords: Stable isotope tracers ; carbon ; nitrogen ; mangroves ; litterfall ; suspended matter ; zooplankton ; macrobenthos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Stable carbon isotopic composition and C/N ratio were used to trace the input of carbon associated with mangrove litter into the estuary of the Godavari–Gautami delta system and Kakinada bay (Andhra Pradesh, India). Suspended organic matter in the mangrove channels was more depleted in 13C (average δ13C = −24.5‰) than in Kakinada bay which showed δ13C values for suspended matter (average δ13C = −22.7‰) closer to those expected for marine phytoplankton. Suspended organic matter from mangrove channels was enriched in nitrogen (average C/N atom ratio ≤ 12.7) and 13C (average δ13C = −24.5‰) relative to mangrove leaf litter, which had a C/N ratio of 75 and a δ13C value of −28‰. Lowest C/N ratios for suspended matter were observed during southwest monsoon when rainfall was highest. Although in general, mangrove litter fall was also lower during this period, no clear correlation was observed between litter fall and C/N ratio of suspended matter. In general, the composition of suspended matter pointed towards phytoplankton as a major component. Isotopic composition of zooplankton suggested selective feeding on 13C-enriched, marine phytoplankton in open Kakinada bay and on 13C-depleted organic matter, such as estuarine phytoplankton and mangrove litter, in the mangrove channels. From the δ13C signature, it appeared that mangrove carbon was present to some extent in zooplankton and macrofauna from the mangrove mudflats and channels, but the signal rapidly decreased in Kakinada bay. Nitrogen isotopic composition of zooplankton and macrofauna indicated a progressive enrichment of 15N away from the mangrove forest towards the northern part of Kakinada bay, in approach of Kakinada city. This is thought to reflect input of anthropogenic nitrogen enriched in 15N and subsequent uptake of this enriched nitrogen into the aquatic food chain.
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  • 39
    ISSN: 1572-8862
    Keywords: acetylene ion ; complex ; hydrogen ; nitrogen ; argon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The complexes formed by the positive acetylene ion with the hydrogen molecule, the nitrogen molecule, and the argon atom are investigated with ab initio calculations using the 6-311G** and the 6-31+G(2df,2pd) basis sets. MP2/6-311G** energies and optimum geometries are obtained, as well as single-point MP3, MP4, and QCISD(T) energies with the MP2/6-311G** optimized geometries. Single-point calculations are performed with the 6-31+G(2df,2pd) basis set at MP2/6-311G** optimized geometries.
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  • 40
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    Agroforestry systems 50 (2000), S. 59-75 
    ISSN: 1572-9680
    Keywords: below-ground competition ; carbohydrates ; nitrogen ; nutrient leaching ; resin cores
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Tree pruning is a common management practice in agroforestry for mulching and reducing competition between the annual and perennial crop. The below-ground effects of pruning, however, are poorly understood. Therefore, nutrient dynamics and root distribution were assessed in hedgerow plantings of Acacia saligna (Labill.) H.L. Wendl. after tree pruning. Pruning to a height of 1.5 m was carried out in March and September 1996. In July and October 1996, the fine root distribution (〈 2 mm) and their carbohydrate contents were determined at three distances to the tree row by soil coring. At the same time, foliar nutrient contents were assessed, whereas nutrient leaching was measured continuously. The highest root length density (RLD) was always found in the topsoil (0–0.15 m) directly under the hedgerow (0–0.25 m distance to trees). Pruning diminished the RLD in the acacia plots at all depths and positions. The relative vertical distribution of total roots did not differ between trees with or without pruning, but live root abundance in the subsoil was comparatively lower when trees were pruned than without pruning. In the dry season, the proportion of dead roots of pruned acacias was higher than of unpruned ones, while the fine roots of unpruned trees contained more glucose than those of pruned trees. Pruning effectively reduced root development and may decrease potential below-ground competition with intercropped plants, but the reduction in subsoil roots also increased the danger of nutrient losses by leaching. Leaching losses of such mobile nutrients as NO3− were likely to occur especially in the alley between pruned hedgerows and tended to be higher after pruning. The reduced size of the root system of pruned acacias negatively affected their P and Mn nutrition. Pruning also reduced the function of the trees as a safety net against the leaching of nutrients for both NO3− and Mn, though not for other studied elements. If nutrient capture is an important aim of an agroforestry system, the concept of alley cropping with pruning should be revised for a more efficient nutrient recycling in the system described here.
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  • 41
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    Landscape ecology 15 (2000), S. 187-199 
    ISSN: 1572-9761
    Keywords: BOD5 ; catchment ; empirical model ; land use change ; land use scenarios ; nitrogen ; phosphorus ; runoff ; SO4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Due largely to unprecedented land-use changes in the Porijõgi River catchment (southern Estonia) losses of nutrients and organic matter have decreased significantly. During the period 1987–1997 abandoned lands increased from 1.7 to 10.5% and arable lands decreased from 41.8 to 23.9%. At the same time, the runoff of total-N, total-P, SO4 and organic matter (after BOD5) decreased from 25.9 to 5.1, 0.32 to 0.13, 78 to 48, and 7.4 to 3.5 kg ha−1 yr−1, respectively. The most significant decreases occurred in agricultural subcatchments while the changes were insignificant in the forested upper course catchment. A simple empirical model which incorporates land-use pattern, fertilization intensity, soil parameters and water discharge accurately described the variations of total-N and total-P runoff in both the whole catchment and its agricultural subcatchments (R 2 varies from 0.95–0.99 for N to 0.49–0.93 for P). In small agricultural subcatchments the rate of fertilization is found the most important factor for nitrogen runoff, whereas in larger mosaic watersheds land use pattern plays the main role. Seven alternative scenarios compiled on the base of the empirical model allow to forecast potential nitrogen and phosphorus losses from the catchment. This information can be used in further landscape and regional planning of the whole region.
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  • 42
    ISSN: 1572-9680
    Keywords: biomass transfer ; integrated nutrient management ; nitrogen ; nutrient cycling ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Tithonia diversifolia, a shrub in the family Asteraceae, is widely distributed along farm boundaries in the humid and subhumid tropics of Africa. Green biomass of tithonia has been recognized as an effective source of nutrients for lowland rice (Oryza sativa) in Asia and more recently for maize (Zea mays) and vegetables in eastern and southern Africa. This paper reviews the potential of tithonia green biomass for soil fertility improvement based on recent research in western Kenya. Green leaf biomass of tithonia is high in nutrients, averaging about 3.5% N, 0.37% P and 4.1% K on a dry matter basis. Boundary hedges of sole tithonia can produce about 1 kg biomass (tender stems + leaves) m−1 yr−1 on a dry weight basis. Tithonia biomass decomposes rapidly after application to soil, and incorporated biomass can be an effective source of N, P and K for crops. In some cases, maize yields were even higher with incorporation of tithonia biomass than with commercial mineral fertilizer at equivalent rates of N, P and K. In addition to providing nutrients, tithonia incorporated at 5 t dry matter ha−1 can reduce P sorption and increase soil microbial biomass. Because of high labor requirements for cutting and carrying the biomass to fields, the use of tithonia biomass as a nutrient source is more profitable with high-value crops such as vegetables than with relatively low-valued maize. The transfer of tithonia biomass to fields constitutes the redistribution of nutrients within the landscape rather than a net input of nutrients. External inputs of nutrients would eventually be required to sustain production of tithonia when biomass is continually cut and transferred to agricultural land.
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  • 43
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    International journal of thermophysics 21 (2000), S. 983-997 
    ISSN: 1572-9567
    Keywords: acoustic resonator ; argon ; Greenspan viscometer ; helium ; helium-xenon mixture ; methane ; nitrogen ; speed of sound ; viscosity of gases ; xenon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract An improved Greenspan acoustic viscometer (double Helmholtz resonator) was used to measure the viscosity of gases at temperatures from 250 to 400 K and at pressures up to 3.4 MPa. The improvements include a vibration damping suspension and the relocation of the fill duct. The fill duct, which is needed to supply gas to the resonator, was connected to the center of the resonator to eliminate acoustic coupling between the resonator and the manifold. In anticipation of handling corrosive gases, all surfaces of the apparatus that are exposed to the test gas are made of metal. The viscometer was tested with argon, helium, xenon, nitrogen, and methane. Isothermal measurements were carried out at 298.15 and 348.15 K and at pressures up to 3.2 MPa. Without calibration, the results differed from published viscosity data by −0.8% to +0.3% (0.47% r.m.s.). These results are significantly better than previous results from Greenspan viscometers. The measurements also yielded the speed of sound, which differed from literature data by +0.16% to +0.20% (0.18% r.m.s.). Adding empirical effective-area and effective-volume corrections to the data analysis decreased the r.m.s. deviations to 0.12% for the viscosity and to 0.006% for the speed of sound. No unusual phenomena were encountered when the viscometer was tested with a helium-xenon mixture between 250 and 375 K.
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  • 44
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    International journal of thermophysics 21 (2000), S. 1033-1044 
    ISSN: 1572-9567
    Keywords: intermolecular potential ; nitrogen ; speed of sound ; virial coefficients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Speeds of sound in nitrogen were measured at temperatures between 170 and 400 K at amount-of-substance densities between 40 and 400 mol·m−3. From these measurements, second and third acoustic virial coefficients were obtained. The parameters of two- and three-body isotropic intermolecular potential-energy models were optimized in a simultaneous fit to the second and third acoustic virial coefficients and the ordinary second and third virial coefficients of nitrogen reported by Nowak et al. The results, which shows that the acoustic and ordinary virial coefficients are mutually consistent, may be used to predict second and third virial coefficients, and their acoustic counterparts, over a wide range of temperatures. The parameters of an anisotropic site-site potential-energy model were also obtained from a fit to the acoustic and ordinary second virial coefficients alone.
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  • 45
    ISSN: 1573-5036
    Keywords: crop residues ; nitrogen ; organic residues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Experiments were conducted to test a new approach to the 15N isotope dilution technique for estimating crop N uptake from organic inputs. Soils were pre-labelled with 15N fertiliser and a carbon source. These were then incubated until there was stabilisation of the 15N abundance of the inorganic N pool and resumption of inorganic N concentrations. Residues were then applied to the soils and planted with ryegrass (Lolium perenneL.) to determine the nitrogen derived from the residue (Ndfr) using the isotope dilution equations. This method was compared with the direct method, i.e. where 15N-labelled residues were added to the soil and Ndfr in the ryegrass calculated directly. Estimates of percentage nitrogen derived from the residue (%Ndfr) alfalfa (Medicago sativaL.) in the ryegrass, were similar, 22 and 23% for the direct and soil pre-labelling methods, respectively, in the Wechsel sandy loam. Also, estimates of the %Ndfr from soybean (Glycine max (L.) Merr) residues in the Krumbach sandy loam were similar 34% (direct) and 36% (soil pre-labelling approach). However, in the Seibersdorf clay loam, the %Ndfr from soybean was 49% using the direct method and 61% using the soil pre-labelling method; yet Ndfr from common bean residue was 46% using the direct approach and 40% using the pre-labelling, not significantly different (P 〉 0.05). The soil pre-labelling approach appears to give realistic values for Ndfr. It was not possible to obtain an estimate of Ndfr using the soil pre-labelling method from the maize residues (Zea mays L.) in two of the soils, as there was no increase in the total N of the ryegrass over the growing period. This was probably due to microbial immobilisation of inorganic N, as a result of the wide C:N ratio of the residue added. The results suggest that the new soil pre-labelling method is feasible and that it is a potentially useful technique for measuring N release from a wide range or organic residues, but it requires further field-testing.
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  • 46
    ISSN: 1573-5036
    Keywords: carbon ; functional types ; leaf tensile strength ; litter quality ; mass loss ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Litter decomposition, a major determinant of ecosystem functioning, is strongly influenced by the litter quality of different species. We aimed at (1) relating interspecific variation in leaf litter decomposition rate to the functional types different species belong to; and (2) understanding the chemical and/or physical basis for such variation and its robustness to environmental factors. We selected 52 Angiosperms from a climatic gradient in central-western Argentina, representing the widest range of functional types and habitats published so far. Ten litter samples of each species were simultaneously buried for 9 weeks during the 1996 summer in an experimental decomposition bed. Decomposition rate was defined as the percentage of dry mass loss after incubation. Chemical litter quality was measured as carbon (C) content, nitrogen (N) content, and C-to-N ratio. Since tensile strength of litter and living leaves were strongly correlated, the latter was chosen as an indicator of physical litter quality. A subset of 15 species representing different functional types was also incubated in England for 15 weeks, following a similar experimental procedure. Litter C-to-N and leaf tensile strength of the leaves showed the strongest negative associations with decomposition rate, both at the species and at the functional-type level. Decomposition rates of the same species in Argentina and in England were strongly correlated. This reinforces previous evidence that species rankings in terms of litter decomposition rates are robust to methodological and environmental factors. This paper has shown new evidence of plant control over the turnover of organic matter through litter quality, and confirms, over a broad spectrum of functional types, general models of resource allocation. The strong correlations between leaf tensile strength – a trait that is easy and quick to measure in a large number of species – decomposition rate, and C-to-N ratio indicate that leaf tensile strength can be useful in linking plant quality to decomposition patterns at the ecosystem level.
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  • 47
    ISSN: 1573-5036
    Keywords: deciduous tree ; foliar pigmentation ; fungus ; litter mass loss ; nitrogen ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We tested the hypothesis that there is a causal connection between autumn colour, nutrient concentration and decomposibility of fresh leaf litter. Samples from patches of different autumn colours within the leaves of the deciduous tree sycamore (Acer pseudoplatanus) were sealed into litter bags and incubated for one winter in an outdoor leaf mould bed. Green leaf patches were decomposed faster than yellow or brown patches and this corresponded with the higher N and P concentrations in the former. Black patches, indicating colonisation by the tar spot fungus Rhytisma acerinum, were particularly high in P, but were decomposed very slowly, owing probably to resource immobilisation by the fungus. The results supported the hypothesis and were consistent with a previous study reporting an interspecific link between autumn coloration and decomposition rate. Autumn leaf colour of deciduous woody plants may serve as a useful predictor of litter decomposibility in ecosystem or biome scale studies where extensive direct measurements of litter chemistry and decomposition are not feasible.
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  • 48
    ISSN: 1573-5036
    Keywords: cereal ; cereal quality ; cereal yields ; natural regeneration ; nitrogen ; nitrogen uptake ; rye-grass ; set-aside ; white clover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract During the period 1993–1997, at six contrasting sites located throughout England, two successive cereal test crops were grown both with and without nitrogen fertiliser after three or five years of set-aside or after continuous arable cropping. Vegetation during set-aside included natural regeneration and perennial rye-grass (Lolium perenne) with or without white clover (Trifolium repens), managed by mowing on one or more occasions per year. Establishment of the successive cereal test crops after destruction of the set-aside was generally not a problem. Fertile tiller numbers were increased by inclusion of clover in the set-aside cover or application of inorganic nitrogen. The presence of couch grass (Elytrigia repens) or volunteer cereals in the set-aside covers provided alternative hosts for take-all (Gaeumanomyces graminis) and eyespot (Pseudocercosporella herpotrichoides) and take-all caused some yield reductions in following cereal crops. Management during the set-aside period significantly affected grain yields of the subsequent cereal crops in the majority of the site-year combinations. However, these effects were not as large as would be expected after traditional break crops and were frequently masked by the application of nitrogen fertiliser. Mean yields increased by 80% due to the application nitrogen at the optimum rate compared to nil nitrogen. Most of the effects of set-aside treatment on grain yield were shown to be attributable to soil mineral nitrogen content, but at some sites, infections by take-all or eyespot also accounted for some of the variation. There were no effects of pests that could be related to treatment. The presence of sown clover during the set-aside period had the most consistent effect across sites, affecting tiller populations, grain yield and grain quality of cereal crops. At some sites, establishing a sown cover during the set-aside period, or cutting the cover more than once a year, improved grain yield and quality, and reduced the incidence of some specific weeds and disease.
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  • 49
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    Plant and soil 219 (2000), S. 273-278 
    ISSN: 1573-5036
    Keywords: cellulose ; lignin ; litter ; nitrogen ; Pinus radiata ; tannins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The quality of substrates in plantation forest litter, and their chemistry, can influence decomposition and N cycling. We studied the decomposition of Pinus radiata D. Don needles suspended on branches in windrows, for 3 yr after clear-cutting, using improved solid-state 13C NMR and chemical analysis. The NMR spectra suggested that the concentration of condensed tannins was 12–22%, and showed they were chemically altered during the period 4–12 months after clear-cutting. The spectra showed no evidence for further chemical modification of the tannins during the second or third years. Data for P. radiata needle decomposition in New Zealand indicated rapid loss of mass in the first 3 months, and condensed tannins did not appear to prevent mineralization of C or N. The tannin and lignin concentrations increased with decomposition of the needles, which was consistent with the early mineralization of readily available C compounds.
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  • 50
    ISSN: 1573-5036
    Keywords: carbon ; defoliation ; nitrogen ; phosphorus ; sheep urine ; soil solution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We have determined the temporal changes in the concentration of dissolved organic carbon (DOC) and P and N components in soil solution following application of synthetic sheep urine (500 kg N ha-1) to a brown forest soil in boxes sown with Agrostis capillaris. Three contrasting defoliation treatments (no cutting, single cut before urine application and regular cutting twice per week) plus a fallow soil were studied. The synthetic urine contained 15N labelled urea and was P-free. Intact soil cores were taken after 2, 7, 14, 21 and 56 d and centrifuged to obtain soil solution. The urea in the synthetic urine was rapidly hydrolysed in the soil, increasing soil solution pH, DOC and total dissolved phosphorus (TDP) concentrations. For the regularly defoliated sward, DOC and P reached maximum concentrations (4000 mg DOC L-1 and 59 mg TDP L-1) on day 7. From their peak values, pH and DOC and P concentrations generally decreased with time and at day 56 were near those of the control. Concentrations of NH4 + and NO3 - in the no-urine treatments fluctuated and the greatest treatment differences were between the fallow soil and the soil sown with grass. Adding synthetic urine increased NH4 + concentrations during the first week, but NO3 - concentrations decreased. This was consistent with the 15N labelling of the NO3 - pool which required 3 weeks to reach that of 15NH4 +. Dissolved organic nitrogen (DON) reached a maximum value at day 7 with a concentration of 409 mg N L-1. The DON in soil solution contained no detectable amounts of 15N label indicating that it was derived from sources in the soil. Differences in soil solution composition related to the effect of the other cutting treatments and the fallow treatment were small compared to the effect of synthetic urine addition.
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  • 51
    ISSN: 1573-5036
    Keywords: ammonia exchange ; apoplast ; atmosphere ; glutamine synthetase ; nitrogen ; photorespiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Plants have a compensation point for NH3 which ranges from 0.1 to 20 nmol mol-1, and may be several-fold higher or lower than naturally occurring atmospheric NH3 concentrations. This implies that NH3 fluxes over vegetated surfaces are bi-directional and that ammonia exchange with the atmosphere in many cases contributes significantly to the nitrogen economy of vegetation. Physiological regulation of plant–atmosphere NH3 fluxes is mediated via processes involved in nitrogen uptake, transport and metabolism. A rapid turnover of NH3 + in plant leaves leads to the establishment of a finite NH3 + concentration in the leaf apoplastic solution. This concentration determines, together with that of H+, the size of the NH3 compensation point. Barley and oilseed rape plants with access to NH3 + in the root medium have higher apoplastic NH3 + concentrations than plants absorbing NO3 -. Furthermore, the apoplastic NH3 + concentration increases with the external NH3 + concentration. Inhibition of GS leads to a rapid and substantial increase in apoplastic NH3 + and barley mutants with reduced GS activity have higher apoplastic NH3 + than wild-type plants. Increasing rates of photorespiration do not affect the steady-state NH3 + or H+ concentration in tissue or apoplast of oilseed rape, indicating that the NH3 + produced is assimilated efficiently. Nevertheless, NH3 emission increases due to a temperature-mediated displacement of the chemical equilibrium between gaseous and aqueous NH3 in the apoplast. Sugarbeet plants grown with NO3 - seem to be temporarily C-limited in the light due to a repression of respiration. As a consequence, the activity of chloroplastic GS declines during the day causing a major part of NH3 + liberated in photorespiration to be assimilated during darkness when 2-oxoglutarate is supplied in high rates by respiration.
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  • 52
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    Plant and soil 223 (2000), S. 47-61 
    ISSN: 1573-5036
    Keywords: correlograms ; nitrogen ; soil arthropods ; soil resource islands ; variograms ; vesicular-arbuscular mycorrhizae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This study compared the sizes, spacings and properties (soil moisture, pH, nitrogen, soil arthropods and VAM) of soil resource islands and bare patches in sagebrush-grass communities invaded by western juniper versus those without juniper. We analyzed 1000 surface soil samples taken from nine 50-m radius circular plots sampled in December of 1991 and May of 1992 on ‘The Island’, one of the few undisturbed areas of sagebrush-grass shrubland in Oregon. Spatial structure was interpreted from correlograms (Moran's I) and standardized semivariograms. The presence of juniper was associated with increased bare area and smaller, more widely spaced grass and sagebrush plants. Soil arthropod numbers and biomass in plots with juniper were only roughly one-fifth of those in sagebrush-grass plots in December. The dominant soil pattern in both sagebrush-grass and juniper-sagebrush-grass plots was regularly-distributed patches spanning a range of sizes and spacings. Plots with juniper had greater patchiness at shorter lags (〈3 m), and patchiness was more developed for soil moisture, net nitrification, and net N mineralization, whereas sagebrush-grass plots had greater patchiness at longer lags (3 – 9 m) and patchiness was more developed for NO3–N, arthropod numbers and biomass. These differences in soil patterns with and without juniper indicate that juniper responds to, or causes, changes in the size of resource islands under sage and grass when it invades sage-grass communities.
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  • 53
    ISSN: 1573-5036
    Keywords: climate change ; immobilisation ; mineralisation ; N-turnover ; nitrogen ; soil organic matter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The following arguments are outlined and then illustrated by the response of the Hurley Pasture Model to [CO2] doubling in the climate of southern Britain. 1. The growth of N-limited vegetation is determined by the concentration of N in the soil mineral N pools and high turnover rates of these pools (i.e., large input and output fluxes) contribute positively to growth. 2. The size and turnover rates of the soil mineral N pools are determined overwhelmingly by N cycling into all forms of organic matter (plants, animals, soil biomass and soil organic matter — `immobilisation' in a broad sense) and back again by mineralisation. Annual system N gains (by N2 fixation and atmospheric deposition) and losses (by leaching, volatilisation, nitrification and denitrification) are small by comparison. 3. Elevated [CO2] enriches the organic matter in plants and soils with C, which leads directly to increased removal of N from the soil mineral N pools into plant biomass, soil biomass and soil organic matter (SOM). ‘Immobilisation’ in the broad sense then exceeds mineralisation. This is a transient state and as long as it exists the soil mineral N pools are depleted, N gaseous and leaching losses are reduced and the ecosystem gains N. Thus, net immobilisation gradually increases the N status of the ecosystem. 4. At the same time, elevated [CO2] increases symbiotic and non-symbiotic N2 fixation. Thus, more N is gained each year as well as less lost. Effectively, the extra C fixed in elevated [CO2] is used to capture and retain more N and so the N cycle tracks the C cycle. 5. However, the amount of extra N fixed and retained by the ecosystem each year will always be small (ca. 5–10 kg N ha-1 yr-1) compared with amount of N in the immobilisation-mineralisation cycle (ca. 1000 kg N ha-1 yr-1). Consequently, the ecosystem can take decades to centuries to gear up to a new equilibrium higher-N state. 6. The extent and timescale of the depletion of the mineral N pools in elevated [CO2] depends on the N status of the system and the magnitude of the overall system N gains and losses. Small changes in the large immobilisation—mineralisation cycle have large effects on the small mineral N pools. Consequently, it is possible to obtain a variety of growth responses within 1–10 year experiments. Ironically, ecosystem models — artificial constructs — may be the best or only way of determining what is happening in the real world.
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  • 54
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    Plant and soil 219 (2000), S. 57-69 
    ISSN: 1573-5036
    Keywords: decomposition ; litter quality ; mycorrhiza ; nitrogen ; phosphorus ; saprotrophic microorganisms ; tannins ; forest soils ; acidification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We studied variation in forest floor thickness in four plantations of red pine (Pinus resinosa Ait.) which were similar in age, soil type and associated vegetation. The plantations were located (west to east) in the Clear Creek, Moshannon, Sproul and Tiadaghton State Forests of Pennsylvania, USA. A gradient in forest floor thickness exists across these plantations; the forest floor is thickest in the west and it becomes progressively thinner toward the east. Decomposition of imported litter increased from west to east, suggesting that the variation in forest floor thickness is related to variation in the rate of decomposition. Decomposition rates were related to saprotroph abundance. Variation in forest floor N and phenolic concentrations, in overall mycorrhiza density and in the relative proportions of three common mycorrhiza morphotypes could not explain the variation in decomposition rate. The P concentrations and pH of the forest floor were significantly lower at Clear Creek and Moshannon, where decomposition rates were lowest, compared to Sproul and Tiadaghton, where decomposition rates were most rapid. This suggests that P concentration and pH may have exerted some control on decomposition.
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  • 55
    ISSN: 1573-5036
    Keywords: carbon ; geostatistics ; nitrification potential ; nitrogen ; pH ; root biomass ; soil respiration ; spatial Heterogeneity ; variability scale
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Geostatistical techniques were used to quantify the scale and degree of soil heterogeneity in 2 m2 plots around 9-year-old poplar trees and within a wheat field. Samples were taken during two years, on an unaligned grid, for analysis of soil respiration, C and N content, available P, gravimetric moisture, pH, nitrification potential, and root biomass. Kriged maps of soil respiration, moisture, and C content showed strong spatial structure associated with poplar trees but not with wheat rows. All soil properties showed higher autocorrelation in June than in April. Isopleth patchiness for all variates was less in June. This was associated with lower respiration rates due to lower litter decomposition. From the degree and scale of heterogeneity seen in this study, we conclude that the main causes of soil heterogeneity at this scale (2 m2) are likely to be found at micro scales controlled in part by plant root and plant residue patterns. These must be understood in the evaluation of ecosystem processes.
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  • 56
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    Plant and soil 225 (2000), S. 153-165 
    ISSN: 1573-5036
    Keywords: carbon ; decomposer food web ; indirect effects ; microbes ; nitrogen ; plant growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We studied the sensitivity of soil microbial communities and ecosystem processes to variation in the vertical and horizontal structure of decomposer food web under nitrogen poor and N-enriched conditions. Microcosms with humus and litter layer of boreal forest floor, birch seedlings infected with mycorrhizal fungi, and decomposer food webs with differing trophic group and species composition of soil fauna were constructed. During the second growing period for the birch, we irrigated half of the microcosms with urea solution, and the other half with de-ionised water to create two levels of N concentration in the substrate. During the experiment night time respirations of the microcosms were measured, and the water leached through the microcosms was analysed for concentration of mineral N, and nematode numbers. The microcosms were destructively sampled after 37 weeks for plant biomass and N uptake, structure of soil animal and microbial community (indicated by PLFA profiles), and physical and chemical properties of the humus and litter materials. Predatory mites and nematodes had a negative influence on the biomass of their microbivorous and microbi-detritivorous prey, and microbi-detritivores affected the biomass and community structure of microbes (indicated by PLFA-analysis). Moreover, predatory mites and nematodes increased microbial biomass and changed the microbial community structure. The decomposer food web structure affected also N uptake and growth of plants. Microbi-detritivorous fauna had a positive effect, whereas predators of microbial and detritus feeding fauna exerted a negative influence on plant N uptake and biomass production. The impact of a trophic group on the microbes and plant was also strongly dependent on species composition within the group. Nitrogen addition magnified the influence of food web structure on microbial biomass and plant N uptake. We suggest that addition of urea-N to the soil modified the animal-microbe interaction by increasing microbial growth and altering community structure of microbes. The presence of microbi-detritivores and predators reduced loss of carbon from the microcosms, and the food web structure influenced also water holding capacity of the materials. The changes in plant growth, nutrient cycling, size of N and C pools, and in the physical properties of the soil emphasize the importance and diversity of indirect consequences of decomposer food web structure.
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  • 57
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    Plant and soil 220 (2000), S. 35-47 
    ISSN: 1573-5036
    Keywords: drainage ; fertilisation ; nature management ; nitrogen ; nutrient contents ; nutrients ; peat ; phosphate ; potassium ; restoration ; rewetting ; shoot biomass ; species richness ; wetlands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Restoration of wet grassland communities on peat soils involves management of nutrient supply and hydrology. The concept of nutrient limitation was discussed as well as its interaction with drainage and rewetting of severely drained peat soils. Different methods of assessing nutrient limitation were compared and the type and extent of nutrient limitation were determined for several wet grassland communities. It was concluded that a full-factorial field fertilisation experiment is the most preferable method. Plant tissue analyses and soil chemical analyses were considered less suitable, although they may provide helpful additional information. Fertilisation experiments in the laboratory using sods or using test plants appear to be the proper means to study mechanisms or processes, but have a restricted predictive value for field situations. Generalising the results, it seems that many relativily undisturbed grassland plant communities on peaty soils are characterised by N limitation. Phosphate limitation for vegetation on peat soils is mainly observed in specific circumstances such as extreme calcium richness, high concentrations of Fe or as a result of drainage or long-term hay cropping. The latter two may also cause K limitation. Rewetting is regarded as a prerequisite in restoring wet grassland communities. Further restoration measures to influence nutrient availability depend on aims of the management and the individual site conditions.
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  • 58
    ISSN: 1573-5036
    Keywords: carbon ; CO2 enrichment ; nitrogen ; particulate organic matter ; roots ; tallgrass prairie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We determined the effects of elevated [CO2] on the quantity and quality of below-ground biomass and several soil organic matter pools at the conclusion of an eight-year CO2 enrichment experiment on native tallgrass prairie. Plots in open-top chambers were exposed continuously to ambient and twice-ambient [CO2] from early April through late October of each year. Soil was sampled to a depth of 30 cm beneath and next to the crowns of C4 grasses in these plots and in unchambered plots. Elevated [CO2] increased the standing crops of rhizomes (87%), coarse roots (46%), and fibrous roots (40%) but had no effect on root litter (mostly fine root fragments and sloughed cortex material 〉500 μm). Soil C and N stocks also increased under elevated [CO2], with accumulations in the silt/clay fraction over twice that of particulate organic matter (POM; 〉53 μm). The mostly root-like, light POM (density ≤1.8 Mg m-3) appeared to turn over more rapidly, while the more amorphous and rendered heavy POM (density 〉1.8 Mg m-3) accumulated under elevated [CO2]. Overall, rhizome and root C:N ratios were not greatly affected by CO2 enrichment. However, elevated [CO2] increased the C:N ratios of root litter and POM in the surface 5 cm and induced a small but significant increase in the C:N ratio of the silt/clay fraction to a depth of 15 cm. Our data suggest that 8 years of CO2 enrichment may have affected elements of the N cycle (including mineralization, immobilization, and asymbiotic fixation) but that any changes in N dynamics were insufficient to prevent significant plant growth responses.
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  • 59
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    Plant and soil 226 (2000), S. 57-69 
    ISSN: 1573-5036
    Keywords: ABA ; K/Na selectivity ; nitrate reduction ; nitrogen ; phloem ; phosphate ; root-shoot interactions ; salinity ; xylem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In this paper four classes of co-operative root-shoot interations are addressed. (I) Nitrogen concentrations in the xylem sap originating from the root and in the phloem sap as exported from source leaves are much lower than those required for growth by apices and developing organs. Enrichment of xylem sap N is achieved by xylem to xylem (X-X) transfer, by which reduced N, but not nitrate, is abstracted from the xylem of leaf traces and loaded into xylem vessels serving the shoot apex. Nitrogen enrichment of phloem sap from source leaves is enacted by transfer of reduced N from xylem to phloem (X-P transfer). Quantitative data for the extent of the contribution of X-X and X-P transfer to the nutrition of young organs of Ricinus communis L. and for their change with time are presented. (II) Shoot and root cooperate in nitrate reduction and assimilation. The partitioning of this process between shoot and root is shifted towards the root under conditions of nitrate- and K-deficiency and under salt stress, while P deficiency shifts nitrate reduction almost totally to the shoot. All four changes in partitioning can be attributed to the need for cation-anion balance during xylem transport and the change in electrical charge occurring with nitrate reduction. (III) Even maintenance of the specificity of ion uptake by the root may – in addition to its need for energy – require a shoot-root interaction. This is shown to be needed in the case of the maintenance of K/Na selectivity under the highly adverse condition of salt stress and absence of K supply from the soil. (IV) Hormonal root to shoot interactions are required in the whole plant for sensing mineral imbalances in the soil. This is shown and addressed for conditions of salt stress and of P deficiency, both of which lead to a strong ABA signalling from root to shoot but result in different patterns of response in the shoot.
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  • 60
    ISSN: 1573-5036
    Keywords: Carbohydrates ; CO2 ; lignin ; nitrogen ; proanthocyanidins ; soil respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Increased atmospheric carbon dioxide (CO2) concentration will likely cause changes in plant productivity and composition that might affect soil decomposition processes. The objective of this study was to test to what extent elevated CO2 and N fertility-induced changes in residue quality controlled decomposition rates. Cotton (Gossypium hirsutum L.) was grown in 8-l pots and exposed to two concentrations of CO2 (390 or 722 μmol mol-1) and two levels of N fertilization (1.0 or 0.25 g l-1 soil) within greenhouse chambers for 8 wks. Plants were then chemically defoliated and air-dried. Leaf, stem and root residues were assayed for total non-structural carbohydrates (TNC), lignin (LTGA), proanthocyanidins (PA), C and N. Respiration rates of an unsterilized sandy soil (Lakeland Sand) mixed with residues from the various treatments were determined using a soda lime trap to measure CO2 release. At harvest, TNC and PA concentrations were 17 to 45% higher in residues previously treated with elevated CO2 compared with controls. Leaf and stem residue LTGA concentrations were not significantly affected by either the elevated CO2 or N fertilization treatments, although root residue LTGA concentration was 30% greater in plants treated with elevated CO2. The concentration of TNC in leaf residues from the low N fertilization treatment was 2.3 times greater than that in the high N fertilization treatment, although TNC concentration in root and stem residues was suppressed 13 to 23% by the low soil N treatment. PA and LTGA concentrations in leaf, root and stem residues were affected by less than 10% by the low N fertilization treatment. N concentration was 14 to 44% lower in residues obtained from the elevated CO2 and low N fertilization treatments. In the soil microbial respiration assay, cumulative CO2 release was 10 to 14% lower in soils amended with residues from the elevated CO2 and low N fertility treatments, although treatment differences diminished as the experiment progressed. Treatment effects on residue N concentration and C:N ratios appeared to be the most important factors affecting soil microbial respiration. The results of our study strongly suggest that, although elevated CO2 and N fertility may have significant impact on post-harvest plant residue quality of cotton, neither factor is likely to substantially affect decomposition. Thus, C cycling might not be affected in this way, but via simple increases in plant biomass production.
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  • 61
    ISSN: 1573-5036
    Keywords: cations ; fire ; nitrogen ; nutrients ; phosphorus ; slash-and-burn ; soil ; tropical forests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The most commonly observed change in soil following slash-and-burn clearing of tropical forest is a short-term increase in nutrient availability. Studies of shifting cultivation commonly cite the incorporation of nutrient-rich ash from consumed aboveground biomass into soil as the reason for this change. The effects of soil heating on nutrient availability have been examined only rarely in field studies of slash-and-burn, and soil heating as a mechanism of nutrient release is most often assumed to be of minor importance in the field. Few budgets for above and belowground nutrient flux have been developed in the tropics, and a survey of results from field and laboratory studies indicates that soils are sufficiently heated during most slash-and-burn events, particularly in dry and monsoonal climates, to cause significant, even substantial release of nutrients from non-plant-available into plant-available forms in soil. Conversely, large aboveground losses of nutrients during and after burning often result in low quantities of nutrients that are released to soil. Assessing the biophysical sustainability of an agricultural practice requires detailed information about nutrient flux and loss incurred during management. To this end, current conceptual models of shifting cultivation should be revised to more accurately describe these fluxes and losses.
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  • 62
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    Plant and soil 219 (2000), S. 177-185 
    ISSN: 1573-5036
    Keywords: alfalfa ; growth ; Medicago sativa L. ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The dynamics of biomass and N accumulation following defoliation of alfalfa and the application of N fertilization has rarely been studied under field conditions, particularly in the seeding year. Our objectives were to determine the effect of N fertilization on the dynamics of biomass and N accumulation during the first regrowth of alfalfa in the seeding year, and to determine if a model describing critical N concentration developed for established stands could be used in the seeding year. In two separate experiments conducted in 1992 and 1993, the biomass and N accumulation of alfalfa grown with three N rates (0, 40 and 80 kg N ha-1) were determined weekly. Maximum shoot growth was reached with 40 kg N ha-1 in 1992, and maximum shoot growth was not reached with the highest N fertilization rate in 1993. Nitrogen fixation, root N reserves and soil inorganic N uptake when no N was applied were, therefore, not sufficient to ensure non-limiting N conditions, particularly when growth rates were the highest between 14 to 21 d after defoliation. Nitrogen fertilization increased shoot biomass accumulation in the first 21 d of regrowth, biomass partitioning to the shoots and shoot and taproot N concentrations. The model parameters of critical N concentration developed by Lemaire et al. (1985) for established stands of alfalfa were not adequate in the seeding year. The N requirements per unit of shoot biomass produced are greater in the seeding year than on established stands, and this was attributed to a greater proportion of leaves in the seeding year.
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  • 63
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    Environmental monitoring and assessment 63 (2000), S. 431-446 
    ISSN: 1573-2959
    Keywords: aquatic bacteria ; benthic macroinvertebrates ; bioindicator ; eutrophication ; nitrogen ; phosphorus ; stream pollution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract A combination field and laboratorystudy was conducted to evaluate the ability of arecently developed bioindicator to detect detrimentalnutrient conditions in streams. The method utilizesbacterial growth on aquatic insects to determinenutrient impacts. Field investigations indicated thatelevated concentrations of nitrate and phosphate wereassociated with growth of filamentous bacteria oninsect body surfaces, and that there was a significantreduction in the density of major insect taxa in thenutrient-enriched stream reaches. Laboratoryinvestigations confirmed a strong linkage betweenbacterial growth and reduced survival of insects. Survival was examined for insects with bacterialinfestation ranging from 0% to greater than 50%coverage of the body surface. A threshold forcatastrophic mortality occurred at about 25% bodycoverage; there were few survivors above that amount. Based on these findings, the diagnostic endpoint forthe bioindicator is 25% body coverage by bacterialgrowth, a level that signifies major impacts and isalso easy to detect visually. This study providesadditional evidence that the insect-bacteriabioindicator is a reliable tool for assessing nutrientimpacts on stream macroinvertebrate communities. Thebioindicator should prove useful for identifyingnutrient-impacted sites as well as monitoring thesuccess of management actions to improve water quality.
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  • 64
    ISSN: 1573-1561
    Keywords: Nicotiana sylvestris ; nitrogen ; nicotine ; allocation ; growth ; reproduction ; induced defenses ; costs of defense
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We present the first evidence for a fitness cost of an inducible response that is detectable in a nitrogen (N) currency. Nicotine is an induced defense in Nicotiana sylvestris that can utilize 5–8% of the plant's total N, an investment that apparently cannot be recouped by metabolism. Induced nicotine production is endogenously regulated by jasmonic acid (JA), and we treated leaves with the methyl ester of this wound hormone (MeJA) in quantities (0, 25, 250 μg) known to elicit changes in endogenous JA and subsequent nicotine responses comparable to those elicited by mechanical wounding and herbivory in this species. We grew plants in competition chambers (CCs) in which three same-sized plants could compete for a communal but fixed pool of 15NO3 to quantify the outcome of competition for this fitness-limiting resource that is used both in defense and seed production. Competition profoundly increased all measures of growth and reproductive performance measured per milligram of N acquired. While plants acquired all the N supplied to them in the hydroponic solution, plants grown in CCs (as compared those grown in individual chambers—ICs) retained more of this N and produced more biomass, had larger nicotine contents, allocated less of their N to nicotine, produced larger floral stalks with more flowers, aborted fewer flowers, matured more capsules, and produced a greater mass of seed. Plants grown in ICs produced heavier seed, but this difference did not translate into a difference in seed viability. MeJA treatment increased nicotine concentrations in proportion to the amount applied and significantly reduced growth (13–23%) and reproductive (31–44%) performance for plants grown with uninduced competitors, reflecting a large opportunity cost of induction. The effects of MeJA treatment on growth and reproduction were significantly less pronounced for plants grown in ICs. MeJA treatment significantly reduced the ability of plants to compete for [15N]KNO3 (reducing uptake by 9.5% and 23.7% for 25- and 250-μg MeJA-treated plants, respectively); no reductions in N acquisition were found in IC grown plants treated with MeJA. This impairment of competitive ability could account for 41–47% of the jasmonate-induced reductions in biomass by the day 15 harvest and 12–20% of the reductions in seed set and, in addition, created by "opportunity benefit" for neighboring uninduced plants, which grew larger, aborted fewer flowers, and matured more seed (a 28% increase) than did uninduced plants competing with similarly uninduced plants. Competition dramatically increased plant growth and reproductive performance, and MeJA treatment of these high-performing plants significantly reduced their competitive ability, which translated into opportunity costs for induced plants and opportunity benefits for neighboring uninduced plants. Induced plants minimized these fitness costs by reducing their use of recently acquired N for nicotine biosynthesis when growing with competitors. MeJA treatments also altered stalk length, flower production, flower abortion, and allocation to seed mass. In spite of all this plasticity, induced responses incur large fitness costs, costs that could be in part attributed to reductions in competitive ability for N. We conclude that inducibility functions to minimize these costs.
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  • 65
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    Journal of chemical ecology 26 (2000), S. 1749-1763 
    ISSN: 1573-1561
    Keywords: Conversion factor ; free amino acids ; fruits ; Kjeldahl ; nitrogen ; nutrition ; protein ; pulp ; secondary metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Protein content of plant tissues is usually estimated by multiplying total nitrogen by a conversion factor of 6.25. This technique assumes that all nitrogen originates from protein. When applied to fruit pulp, it overestimates protein content because pulp typically contains free amino acids and many nitrogenous secondary metabolites. At issue is the extent of error and, consequently, what the conversion factor between nitrogen and protein should be. We calculated a conversion factor based on pulp samples from 18 species collected in the southeastern United States. We also report a new and simple method of estimating protein and free amino acids in fruit pulp. Because previous studies have found high variation in protein and secondary metabolite content among fruit species, use of a single conversion factor for all species will generate error. In an attempt to reduce such error, we calculated protein contents and conversion factors separately for two common fruit types: lipid-rich/carbohydrate-poor and lipid-poor/carbohydrate-rich. We found no difference between these types of fruit and hence combined results in calculating an average conversion factor of 5.64. Use of an accurate conversion factor is important in estimating protein consumption by wild animals and in formulating diets of captive animals. It can also reveal whether loss of body mass in captive animals on fruit diets is due to insufficient protein consumption, secondary metabolite toxicity, or an imbalance of amino acids.
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  • 66
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    Environmental and resource economics 16 (2000), S. 347-362 
    ISSN: 1573-1502
    Keywords: cost-effectiveness ; nitrogen ; nonpoint ; policy ; value ; wetlands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Economics
    Notes: Abstract Wetlands, in Sweden and elsewhere, have been suggestedas effective and low-cost sinks for agriculturalpollution. This paper estimates the value of usingwetlands for abatement of agricultural nitrogen loadon the Baltic Sea. A replacement value of wetlands isestimated for Sweden. The replacement value is definedand estimated as the difference between twocost-effective reductions of agricultural nitrogenpollution: one that uses wetlands for nitrogenabatement, and one that does not. It is shown that theuse of wetlands as nitrogen sinks can reduce the totalabatement costs of nitrogen emissions by 30% forSwedish agricultural sources of nitrogen pollution.
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  • 67
    ISSN: 1573-2932
    Keywords: nitrification ; nitrogen ; nitrogen mineralization ; soil water ; stream chemistry ; wilderness area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Nitrogen (N) deposition and its impact on terrestrial and aquatic ecosystems is a concern facing federal land managers at the Lye Brook Wilderness in Vermont and other protected aras throughout the northeastern United States. In this study, we compared N production in soils with N concentrations and outputs in leachates to determine how forest cover types differ in regulating N losses. Also, precipitation inputs and modeled estimates of streamwater outputs were used to calculate a watershed N budget. Most ammonium and nitrate were produced in organic soils with deciduous cover. Softwood stands had low net nitrification rates and minimal N leaching. A comparison of watershed inputs and outputs showed a net gain in total dissolved N (5.5 kg ha-1 yr-1) due to an accumulation of dissolved inorganic N. The Lye Brook Wilderness ecosystem has N budgets similar to other forested ecosystems in the region, and appears to be assimilating the accumulating N. However seasonal losses of nitrate observed in mineral soils and streamwater may be early warnings of the initial stages of N saturation.
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  • 68
    ISSN: 1573-2932
    Keywords: on-site treatment ; fecal coliform bacteria ; nitrate leaching ; nitrogen ; on-site treatment ; septic effluent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Groundwater effluent sample collectors(zero-tension lysimeters) were installed directlybelow the drainfields of three residential onsitetreatment systems in the Clover/Chambers Creek aquiferregion of Pierce County near Tacoma, WA. The use of asplit effluent delivery system from the septic tank,where half the effluent was delivered under pressureto a normal native soil-only filter system and halfwas delivered to a sand filter system, allowed thedirect comparison of the two commonly-utilized septicsystems for treatment levels. Septic tank effluent(from the septic tank) and percolating water (between0.3 and 0.9 m beneath the effluent distributionlines) was collected between May 1991 and April 1994on 30 occasions. Samples were analyzed for fecalcoliform bacteria, nitrate, nitrite, ammonium andtotal reduced (Kjeldahl) nitrogen. Results of thisstudy indicate that the use of sand filters greatlyincreased removal of fecal coliform bacteria and totalnitrogen. Soil-only filter systems had an average of91% removal of fecal coliforms and 47%of total N; whereas sand filter systems had an averageof 99.8% removal of fecal coliforms and 80% of total N.
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  • 69
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    Plasma chemistry and plasma processing 20 (2000), S. 87-110 
    ISSN: 1572-8986
    Keywords: striations ; nitrogen ; spherical discharge ; spatially inhomogeneous Boltzmann equation ; electron velocity distribution function ; dc glow discharge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract Recent observations of spherical striations in large-volume nitrogen dcdischarges with a central anode have stimulated investigations of thenonlocal electron kinetics in these striations by solving the spatiallyinhomogeneous Boltzmann equation adapted to spherical geometry. Becausethe radial course of the electric potential is largely unknown in thisdischarge, different models concerning its radial course have been developedand used. These models are based on the measured radii of the striationsand the assumption that the potential drop between successive striationsdoes not change. As a consequence, with decreasing distance between thestriations the electric field strongly increases toward the centralanode. It has been found that spherical striations are only obtained ifthe electric field is strongly modulated. In this case, a highly nonlocalbehavior of the velocity distribution function and strongly modulatedradial courses of the macroscopic quantities have been obtained.
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  • 70
    ISSN: 1573-2932
    Keywords: eutrophication ; nitrogen ; phosphorus ; river ; sediment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Nitrogen (N) and phosphorus (P) concentrations were determined in sediment samples along the bed of Catatumbo river in both Colombian and Venezuelan territories until the river outlet in Maracaibo lake. Total phosphorus was determined by digestion with HCl followed by analysis using the ascorbic acid method and total nitrogen was done using the standard microkjeldahl method plus nitrate-nitrite. Ammonium, orthophosphate and nitrate were determined using standard methods after extraction steps. The mean concentrations along the river bed were found in an interval of 0.035 and 1.492 mg g-1 dry sed. for nitrogen and 0.027 and 1.039 mg g-1 dry sed. for phosphorus at 95% confidence level. The mean molar ratio N/P in the river bed was 4.42 and 3.46 for river outlet zones in the lake, which indicates that nitrogen is the limiting nutrient. For comparison with previous results of lake sediments from sites near the river outlet it was concluded that Catatumbo river is a significant source of nutrients to the Maracaibo Lake system because sediment nutrients concentrations from Catatumbo river were higher than the ones in Maracaibo Lake. Statistic studies showed significant differences between countries, zones and similar behaviour in the river bed as related to the affluent rivers.
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  • 71
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    Water, air & soil pollution 119 (2000), S. 121-137 
    ISSN: 1573-2932
    Keywords: nitrogen ; wet deposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract We measured concentrations and fluxesof major ions in wet deposition, throughfall andstream water in a forested watershed on the AlleghenyPlateau of western Maryland to investigatecanopy-atmosphere interactions and to calculate input–output budgets. Wet deposition was dominated byH+, SO 4 2− , NO 3 − andNH 4 + ions. Hydrogen and SO 4 2− accounted for 70 and 58% of the total cation andanion equivalents, respectively. Annual wet depositionrates of SO 4 2− (0.56 keq ha−1 yr−1), NO 3 − (0.31 keq ha−1 yr −1)and NH 4 + (0.17 keq ha−1 yr −1)were at the high end of the range in wet depositionrates reported for other sites in the eastern UnitedStates. On an annual basis, the forest canopy consumed20% of the free acidity in incident precipitation,had no net effect on Na+ and NH 4 + deposition, and was a net source of K+,Ca2+, Mg2+, SO 4 2− andNO 3 − ; 1.5 to 22 times greater than the wetdeposition rates. On an annual basis, the watershed ofthe unnamed tributary to Herrington Creek (HCWS)retained essentially all of the throughfall H+ andNH 4 + inputs, 35% of the throughfall K+input and 62% of the throughfall NO 3 − input. In contrast, HCWS was a net source ofSO 4 2− , Cl−, Ca2+, Mg2+ andNa+; export rates were 2 to 5 times greater thanthroughfall inputs. Sulfate was the dominant anionassociated with cation leaching, accounting for 78%of the total anion export of 1.8 keq ha−1 yr −1 in 1996–1997.
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  • 72
    ISSN: 1573-1642
    Keywords: nitrogen ; phosphorus ; macroalgae ; estuary ; anthropogenic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Our objective was to begin to investigate sources, sinks, and flux rates of nitrogen (N) and phosphorus (P) in Famosa Slough, a small (12 ha) highly modified urban estuary in San Diego, California, U.S.A. The hydrology of Famosa Slough has been modified by culverts that dampen tidal influence and seasonal runoff from two urban watersheds, each of which has been implicated as a nutrient source that generates nuisance algal blooms. In 1995 and 1996, the ranges of nutrients measured in the water column were extremely wide; upper values exceeded those in other estuaries identified as eutrophic. Average dissolved inorganic nitrogen ranged from 2 to 250 μM, while dissolved inorganic phosphorus ranged from 〈1 to 15 μM. Nutrient content of the water changed rapidly both spatially and temporally depending on the tides and rainfall. While tidal water dominated this system, especially in the dry season, our results indicate that Famosa Slough's small watershed, not the larger watershed of the San Diego River, was the major source of nutrients during rainfall. Sediment nutrients were also high (∼3 mg N g dry wt−1 and 0.600 mg P g dry wt−1). Short-term flux studies suggest that the large accumulations of opportunistic green macroalgae commonly found in this estuary, and possibly the sediments, may act as a large and rapid sink for nutrients during times of high nutrient supply. We suggest that small, shallow estuaries in urban settings may have more complex and rapid nutrient dynamics than those found in larger systems.
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  • 73
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    Investigational new drugs 18 (2000), S. 373-381 
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
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  • 74
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    Journal of applied phycology 12 (2000), S. 331-339 
    ISSN: 1573-5176
    Keywords: algal biomass ; algal uptake ; ammonia stripping ; biological nutrient removal ; high rate algal ponds ; nitrogen ; nutrients ; nitrification ; urban wastewater treatment ; waste stabilisation ponds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Two experimental high rate algal ponds (HRAPs) (1.5m2, 570 L per unit), each with a secondaryclarifier for algal biomass separation (0.025 m2,without recirculation), were fed with urban wastewaterfor a one-year period (June 1993 to July 1994). TheHRAPs were installed on the roof of the Department ofHydraulic, Coastal and Environmental Engineering ofthe Technical University of Catalonia, Barcelona,Spain (lat. 41° 24′ 42″ N; long. 2° 7′42″ E). Nitrogen removal efficiency and changes intotal nitrogen, total organic nitrogen,NH4 +-N, and oxidized nitrogen underdifferent hydraulic retention times (HRTs) werecompared. HRAP A was always operated at a higherHRT than HRAP B. Both HRAPs were subjected to thesame environmental conditions of solar radiation, airtemperature and influent water quality. Grab samplesof influent, effluent of the HRAP (mixed liquor) andfinal effluent from the clarifiers were taken once aweek. The annual average nitrogen removal was 73% forHRAP A, and 57% for HRAP B. Higher removal in HRAP Awas due to a lower inorganic nitrogen concentration inits effluent. Significant differences (p〉 0.05) inthe relative proportions of nitrogen forms between thetwo HRAPs were observed only in autumn and winter.This was mainly because HRAP B did not achieve a highlevel of NH4 +-N removal by stripping andalgal uptake, as observed in HRAP A. NH4 +-Nstripping was the most important mechanism fornitrogen removal (mean efficiency of 47% and 32% inHRAP A and B, respectively) followed by algal uptake,and subsequent algal separation in the clarifiers(mean efficiency of 26% and 25% in HRAP A and Brespectively). The conclusion of this study is thatHRT determines both the nitrogen removal efficiencyand the distribution of nitrogen forms in the effluentof a HRAP. The nitrogen removal level can becontrolled through suitable HRT operating strategies.By operating at a HRT of 4 days in spring and summer,and 10 days in autumn and winter, nitrogenconcentration in the effluent of a HRAP system can bereduced to less than 15 mg L-1 N.
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  • 75
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    Wetlands ecology and management 8 (2000), S. 197-207 
    ISSN: 1572-9834
    Keywords: benthic invertebrates ; mitigation ; nitrogen ; organic matter ; pedogenesis ; phosphorus ; plant productivity ; restoration and rehabilitation ; salt marsh ; wetland creation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The development of wetland soil characteristics andbenthic invertebrate communities were evaluated increated Spartina alterniflorasalt marshes inNorth Carolina ranging in age from 1 to 25 years-old.A combination of measurements from different-agecreated marshes as well as periodic measurements overtime on two marshes were used to (1) document rates ofwetland pedogenesis, especially soil organic matter,and, (2) explore relationships between soil andbenthic invertebrate community development. Soilmacro-organic matter (MOM, the living and dead rootand rhizome mat), organic C and N increased and bulkdensity decreased during the 25 years following marshestablishment. The most dramatic changes in bulkdensity, MOM, C and N occurred within the upper 10 cmof the soil with lesser changes below this depth.Created marshes were sinks for organic C (90–140g·m-2·yr-1) and N (7–11g·m-2·yr-1) but not for P (0–1g·m-2·yr-1). The density of benthicinvertebrates (〉250 μm) and subsurface-depositfeeding oligochaetes also increased over time oncreated salt marshes. Invertebrate and oligochaetedensity were strongly related to MOM content(r2= 0.83–0.87) and soil organic C(r2= 0.52–0.82) and N (r2= 0.62–0.84). Thesefindings suggest that, in created salt marshes,development of the benthic invertebrate community istied to marsh soil formation, especially accumulationof organic matter as MOM and soil. Field studies thatmanipulate the quantity and quality of soil organicmatter are needed to elucidate the relationshipbetween salt marsh pedogenesis and benthicinvertebrate community development.
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  • 76
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    Plant cell, tissue and organ culture 61 (2000), S. 59-67 
    ISSN: 1573-5044
    Keywords: alar ; in vitro plantlet ; mannitol ; nitrogen ; rooting ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The importance of leaf area of in vitro propagated potato (Solanum tuberosum L.) plantlets for further growth during acclimatisation and the after-effects of in vitro treatments on growth were examined. The in vitro treatments included different levels of alar, nitrogen or mannitol or different temperatures during the last in vitro phase, the rooting phase. Leaf area or ground cover was recorded one day after planting to soil and at the end of the first phase of ex vitro growth, the acclimatisation phase. Regression analysis showed that leaf area of a transplant at the end of acclimatisation phase was positively influenced by leaf area of the same plantlet at the beginning of the phase. The relative increase in leaf area during acclimatisation (increase/early leaf area) was linearly related to the inverse of the early leaf area, indicating almost comparable relative increases for plantlets having larger early leaf areas, but more variable responses for plantlets having smaller early leaf areas. In vitro treatments mainly affected leaf area of transplants through their effects on early leaf area. Adding alar, reducing nitrogen and reducing temperature increased leaf area. Reducing mannitol increased ground cover. A lower nitrogen concentration and higher temperature in some cultivars had slight negative effects on the relative increase in leaf area after acclimatisation. For nitrogen these negative effects were less significant than the positive effects through early leaf area. Results stress the importance of manipulation of leaf area in vitro to enhance plant performance in later stages of growth.
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  • 77
    ISSN: 1573-8469
    Keywords: carbon ; cellulose ; cover crop ; damping-off ; discriminant analysis ; lignin ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Stages of oat–vetch cover crop decomposition were characterized over time in terms of carbon and nitrogen cycling, microbial activity and damping-off pathogen dynamics in organically and conventionally managed soils in a field and a controlled incubation experiment. A measurement of relative growth consisting of radial growth of a fungal colony over non-sterilized soil divided by that over sterilized soil was used as an assay of suppressiveness. No differences in relative growth of Pythium aphanidermatum and Rhizoctonia solani were detected between organic and conventionally managed soils amended with cover crop residue. Significant effects of cover crop decomposition stage on the relative growth of both pathogens were obtained. Relative growth of P. aphanidermatum was highest just after incorporation and decreased 3 weeks after incorporation. Relative growth of R. solani was highest about 20 days after incorporation, and decreased 2 weeks later in the organic system, but continued to increase in the conventional system. In both experiments, the N or C content, C:N ratio or dry weight of retrieved debris were significantly correlated with relative growth of P. aphanidermatum. Relative growth of R. solani was significantly correlated with the C:N ratio of soil or the C or N content of debris. Microbial activity was not consistently associated with relative growth of either pathogen.
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  • 78
    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
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  • 79
    ISSN: 1573-9058
    Keywords: carbon ; C/N ; direct and indirect effects ; nitrogen ; soluble sugars ; starch ; specific leaf area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Dark respiration rate in the night (R D) was measured in five-year-old Scots pine (Pinus sylvestris L.) trees grown for two years under ambient (AC) and elevated (AC + 400 µmol mol−1 = EC) CO2 concentrations in open top chambers. Two needle age classes (i.e., current-year and one-year-old) were measured at AC and EC in both AC- and EC-grown pines. Additionally different chemical characteristics were determined on the needles, such as nitrogen (N), carbon (C), starch, and soluble sugar concentrations as well as specific leaf area. The direct, short-term and indirect, long-term effects of EC on R D for the two needle age classes were examined. R D was expressed on a per needle area, needle mass, N, C, and C/N bases. Direct effects were only pronounced in the AC treatment where inhibition of R D was found at EC in both current- and one-year-old needles. Indirect effects were only significant in one-year-old needles where a decrease was found in the EC grown trees as compared with AC ones when R D was expressed per unit needle mass, C, or C/N. R D per unit needle area and needle N were not sensitive to long-term EC, in any needle age class. Long-term EC treatment also influenced the response of the two needle age classes. One-year-old needles from the EC treatment had significantly lower R D than current-year needles, but no such response was observed in the AC treatment. Our experiment re-emphasised the importance of expressing R D on different bases for a correct interpretation of the responses to EC. Moreover, we showed that different needle age classes can respond differently to a CO2 enrichment.
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  • 80
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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  • 81
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 82
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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  • 83
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 84
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    Journal of materials synthesis and processing 7 (1999), S. 311-319 
    ISSN: 1573-4870
    Keywords: Iron ; carbon ; nitrogen ; microstructure ; characterization ; HIP-drip
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A new processing technique makes nitrogen alloying possible by adding nitrogen under elevated nitrogen pressure to prealloyed Fe-C ingots during continuous casting, producing a whole new class of precipitation-free, iron–carbon–nitrogen alloys. When both carbon and nitrogen bulk concentration levels exceeded 0.5 wt%, a duplex fcc-/(bcc-bct-) Fe microstructure resulted that is iron carbide- and nitride-free. With increasing carbon and nitrogen concentrations, there was an increase in the retained fcc-Fe phase. In cooling rate studies, increasing carbon and nitrogen concentrations shifted the knee of the fcc-Fe-to-bcc-Fe phase time–temperature–transformation (T–T–T) curve to longer times. Hardness, compression strength, and wear resistance increased with increasing carbon and nitrogen concentrations and were superior to iron–carbon alloys without the nitrogen addition.
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  • 85
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    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 491-512 
    ISSN: 1573-8744
    Keywords: muscle relaxants ; peripheral elimination ; pharmacokinetics ; peripheral concentrations ; volume of distribution ; pharmacokinetic model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: 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.
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  • 86
    ISSN: 1573-904X
    Keywords: antisense ; Brown-Norway rat ; oligodeoxynucleotide ; pulmonary delivery ; ISIS 2105 ; pharmacokinetics ; airway inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate the pulmonary distribution of CGP69846A (ISIS 5132), a phosphorothioate oligonucleotide, following intra-tracheal (i.t.) instillation into Brown-Norway rats. Methods. The pharmacokinetic profile of [3H]-CGP69846A was investigated following i.t. instillation into both naïve and inflamed airways of Brown-Norway rats. The cellular distribution was determined using autoradiography, immunohistochemistry and flow cytometry/fluorescence microscopy, in inflamed airways. Results. CGP69846A displayed a dose-dependent lung retention following i.t. administration which was unaffected by local inflammation. Autoradiography and immunohistochemistry showed distribution to alveolar macrophages, eosinophils, bronchial and tracheal epithelium and alveolar cells. Studies with [FITCJ-CGP69846A demonstrated a preferential association of oligonucleotide with leukocytes in bronchial lavage fluid of: macrophages 〉 eosinophils = neutrophils 〉 〉 lymphocytes. Conclusions. The dose-dependency of lung retention together with cell-specific uptake suggests that the lung can be used as a local target for antisense molecules with potentially minimal systemic effects. Furthermore, the preferential targeting of macrophages and the airway epithelium by oligonucleotides may represent rational cellular targets for antisense therapeutics.
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  • 87
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; Calphostin C ; HPLC ; perylenequinone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To examine the pharmacokinetic features and metabolism of calphostin C, a naturally occurring perylenequinone with potent antileukemic activity. Methods. HPLC-based quantitative detection methods were used to measure calphostin C levels in lysates of leukemic cells and in plasma of mice treated with calphostin C. The plasma concentration-time data were analyzed using the WinNonlin program. In vitro esterases and a microsome P450 preparation in conjunction with a LC-MS(API-EI) system were used to study the metabolism of calphostin C. Results. An intracellular exposure level (AUC0−6h) of 257 μM·h was achieved after in vitro treatment of NALM-6 cells with calphostin C at a 5 μM final concentration in culture medium. After intraperitoneal (i.p.) injection of a 40 mg/kg nontoxic bolus dose of calphostin C, the estimated Cmax was 2.9 μM, which is higher than the effective in vitro concentration of calphostin C against leukemic cells. Drug absorption after i.p. administration was rapid with an absorption half-life of 24.2 min and the estimated tmax was 63.0 min. Calphostin C was cleared with an elimination half-life of 91.3 min. An inactive and smaller metabolite (calphostin B) was detected in plasma of calphostin C-treated mice with a tmax of 41.3 min. Esterase (but not P450) treatment of calphostin C in vitro yielded an inactive metabolite (calphostin B) of the same size and elution profile. Conclusions. Target plasma calphostin C concentrations of potent antileukemic activity can be reached in mice at nontoxic dose levels. This pilot pharmacokinetic study of calphostin C combined with the availability of the described quantitative HPLC method for its detection in cells and plasma provide the basis for future preclinical evaluation of calphostin C and its potential as an anti-leukemic drug.
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  • 88
    ISSN: 1573-904X
    Keywords: diffusion model ; drug delivery system ; ocular penetration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the ocular pharmacokinetics of beta-blockers (timolol and tilisolol) after instillation in the albino rabbit using a mathematical model that includes a diffusion process. Methods. The disposition of fluorescein isothiocyanate-dextran (FITC-dextran, molecular weight 4400), timolol, and tilisolol was determined in tear fluid and aqueous humor after instillation or ocular injection in rabbits. The in vivo penetration parameters were estimated by fitting the concentration-time profiles to the Laplace equations based on a diffusion model using MULTI(FILT) program. Thein vivo permeability of drugs was measured across cornea using a two-chamber diffusion cell. Results. Concentration-time profiles of drugs in the tear fluid after instillation showed a monoexponential curve. Although a monoexponential curve was observed in the aqueous humor concentration of FITC-dextran after injection into the aqueous chamber, timolol and tilisolol showed a biexponential curve. On the basis of these results, anin vivo pharmacokinetic model was developed for estimation of penetration parameters. The in vitro partition parameters were higher than those of the in vivo parameters. Conclusions. The ocular absorption of timolol and tilisolol was characterized using an in vivo pharmacokinetic model and in vivo penetration parameters.
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  • 89
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    Pharmaceutical research 16 (1999), S. 1608-1615 
    ISSN: 1573-904X
    Keywords: tenidap ; pharmacokinetics ; EM algorithm ; nonlinear mixed-effects modelling ; covariates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a pharmacokinetic model for tenidap and to identify important relationships between the pharmacokinetic parameters and available covariates. Methods. Plasma concentration data from several phase I and phase II studies were used to develop a pharmacokinetic model for tenidap, a novel anti-rheumatic drug. An appropriate pharmacokinetic model was selected on the basis of individual nonlinear regression analyses and an EM algorithm was used to perform a nonlinear mixed-effects analysis. Scatter plots of posterior individual pharmacokinetic parameters were used to identify possible covariate effects. Results. Predicted responses were in good agreement with the observed data. A bi-exponential model with zero order absorption was subsequently used to develop the mixed-effects model. Covariate relationships selected on the basis of differences in the objective function, although statistically significant, were not particularly strong. Conclusions. The pharmacokinetics of tenidap can be described by a bi-exponential model with zero order absorption. Based on differences in the log-likelihood, significant covariate-parameter relationships were identified between smoking and CL, and between gender and Vss and CLd. Simulated sparse data analyses indicated that the model would be robust for the analysis of sparse data generated in observational studies.
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    Pharmaceutical research 16 (1999), S. 176-185 
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; pharmacodynamics ; pharmacology ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacokinetic/pharmacodynamic (PK/PD)-modeling links dose-concentration relationships (PK) and concentration-effect relationships (PD), thereby facilitating the description and prediction of the time course of drug effects resulting from a certain dosing regimen. PK/PD-modeling approaches can basically be distinguished by four major attributes. The first characterizes the link between measured drug concentration and the response system, direct link versus indirect link. The second considers how the response system relates effect site concentration to the observed outcome, direct versus indirect response. The third regards what clinically or experimentally assessed information is used to establish the link between concentration and effect, hard link versus soft link. And the fourth considers the time dependency of pharmacodynamic model parameters, distinguishing between time-variant versus time-invariant. Application of PK/PD-modeling concepts has been identified as potentially beneficial in all phases of preclinical and clinical drug development. Although today predominantly limited to research, broader application of PK/PD-concepts in clinical therapy will provide a more rational basis for patient-specific dosage individualization and may thus guide applied pharmacotherapy to a higher level of performance.
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  • 91
    ISSN: 1573-904X
    Keywords: aminolevulinic acid ; intravesical ; pharmacokinetics ; photodiagnosis ; bladder ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To examine the stability and systemic absorption of aminolevulinic acid (ALA) in dogs during intravesical administration. Methods. Nine dogs received an intravesical dose of ALA either with no prior treatment, after receiving ammonium chloride for urinary acidification, or after receiving sodium bicarbonate for urinary alkalinization. Urine and blood samples collected during and after administration were monitored for ALA using an HPLC assay developed in our laboratories. Concentrations of pyrazine 2,5-dipropionic acid, the major ALA degradation product, and radiolabeled inulin, a nonabsorbable marker for urine volume, were also determined. Results. Less than 0.6% of intravesical ALA doses was absorbed into plasma. Urine concentrations decreased to 37% of the initial concentration during the 2 hour instillation. Decreases in urinary ALA and radiolabeled inulin concentrations were significantly correlated, indicating that urine dilution accounted for over 80% of observed decreases in urinary ALA. ALA conversion to pyrazine 2,5-dipropionic acid was negligible. Conclusions. These studies demonstrate that ALA is stable and poorly absorbed into the systemic circulation during intravesical instillation. Future studies utilizing intravesical ALA for photodiagnosis of bladder cancer should include measures to restrict fluid intake as a means to limit dilution and maximize ALA concentrations during instillation.
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  • 92
    ISSN: 1573-904X
    Keywords: bezafibrate ; hyperlipidemia ; pharmacodynamics ; pharmacokinetics ; sustained release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate the role of different routes and modes of administration of bezafibrate (BZF) on its hypolipidemic activity. We hypothesize that the major sites of BZF action are located presystemically as in other 'gastrointestinal (GI) drugs.' Thus, continuous administration of the drug to the GI tract is expected to augment its efficacy and provides a rationale for an oral sustained release preparation of the drug. Methods. The hypothesis was investigated in three experimentally induced-hyperlipidemia rat models. Models A and B were based on cholesterol-enriched diets and Model C on induced acute hyperlipidemia by triton 225 mg/kg. The pharmacokinetics and the pharmacodynamics of the drug following various modes of administration were examined. Results. In all cases, continuous administration of the drug into the duodenum (IGI) at a dose of 30 mg/kg/day for 3 days (Models A and B) or over 18 hr (Model C) reduced significantly both total cholesterol and triglycerides levels and elevated HDL cholesterol levels in comparison to bolus oral administration of the same dose, as well as in comparison to equivalent intravenous infusion (Model C). Infusion of the drug directly into the portal vein produced an equivalent activity to IGI administration. The pharmacokinetic study showed 100% oral bioavailability, good colonic absorption properties and an indication for an enterohepatic cycle. Conclusions. The results confirm that BZF has a first pass hepatic pharmacodynamic effect. Administration of BZF in a slow release matrix tablet to the rats produced the same magnitude of effect as IGI administration, thus proving the pharmacodynamic rationale for this mode of administration for GI drugs.
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  • 93
    ISSN: 1573-904X
    Keywords: C6-glioma ; methotrexate ; microdialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Establishment of the pharmacokinetic profile of methotrexate (MTX) in the extracellular fluid (ECF) of a brain C6-glioma in rats. Methods. Serial collection of plasma samples and ECF dialysates after i.v. infusion of MTX (50 or 100 mg/kg) for 4 h. HPLC assay. Results. Histological studies revealed the presence of inflammation, edema, necrosis, and hemorrhage in most animals. In vivo recovery (reverse dialysis) was 10.8 ± 5.3%. MTX concentrations in tumor ECF represented about 1−2% of the plasma concentrations. Rapid equilibration between MTX levels in brain tumor ECF and plasma. ECF concentrations almost reached steady-state by the end of the infusion (4 h), then decayed in parallel with those in plasma. Doubling of the dose did not modify MTX pharmacokinetic parameters (t1/2α, t1/2β, MRT, fb, Vd, and CLT), except for a 1.7-fold increase of AUCPlasma and a 3.8-fold increase in AUCECF which resulted in a 2.3-fold increase in penetration (AUCECF/AUCPlasma). In spite of an important interindividual variability, a relationship between MTX concentrations in plasma and tumor ECF could be established from mean pharmacokinetic parameters. Conclusions. High plasma concentrations promote the penetration of MTX into brain tissue. However, free MTX concentrations in tumor ECF remain difficult to predict consistently.
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  • 94
    ISSN: 1573-904X
    Keywords: HI-240 ; nonnucleoside inhibitor ; pharmacokinetics ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of the present study was to examine the pharmacokinetic features and tissue distribution of N-[2-(2-fluorophenethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (HI-240), a novel non-nucleoside inhibitor of HIV reverse transcriptase with potent anti-viral activity against AZT-sensitive as well as multidrug-resistant HIV-1 strains. Methods. A sensitive and accurate high performance liquid chromatography (HPLC)-based quantitative detection method was established to measure concentrations of HI-240 in pharmacokinetic studies. The plasma concentration-time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameter values. Results. HI-240 had an elimination half-life of 78.3 ± 2.0 min after i.v. administration and 196.8 ± 3.1 min after i.p. administration. The systemic clearance of HI-240 was 2194 ± 61 ml/h/kg after i.v. administration and 9339 ± 1160 ml/h/kg after i.p. administration. Following i.v. injection, HI-240 rapidly distributed to and accumulated in multiple tissues with particularly high accumulation in adipose tissue, adrenal gland, and uterus+ovary. The concentration of HI-240 in brain tissue was comparable to that in the plasma, indicating that HI-240 easily crosses the blood-brain-barrier. Following i.p. injection, HI-240 was rapidly absorbed with a t1/2ka and a tmax values of less than 10 min. Following oral administration, HI-240 was absorbed with a t1/2ka of 4.2 ±1.1 min and a tmax of 95.1 ± 25.1 min. The intraperitoneal bioavailability was estimated at 23.5%, while the oral bioavailability was only 1%. Conclusions. The HPLC-based accurate and precise analytical detection method and pilot pharmacokinetic studies described herein provide the basis for advanced preclinical pharmacodynamic studies of HI-240. The ability of HI-240 to distribute rapidly and extensively into extravascular compartments and easily cross the blood-brain barrier represent significant pharmacokinetic advantages over AZT.
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  • 95
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 16 (1999), S. 261-265 
    ISSN: 1573-904X
    Keywords: crystal habit ; trimethoprim suspension ; physical stability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The role of crystal habit in influencing the physical stability and pharmacokinetics of trimethoprim suspensions was examined. Methods. Different habits of trimethoprim (TMP) were obtained by recrystallizing the commercial sample (PD) utilizing solvent-change precipitation method. Four distinct habits (microscopic observation) belonging to the same polymorphic state (DSC studies) were selected for studies. Preformulation and formulation studies were carried out on suspension dosage forms containing these crystals. The freshly prepared suspensions were also evaluated for their pharmacokinetic behaviour on healthy human volunteers using a cross over study. Results. Variation of crystallization conditions produces different habits of TMP. Among the different crystal habits exhibiting same polymorphic state, the most anisometric crystal showed best physical stability in terms of sedimentation volume and redispersibility. However, habit did not significantly affect the extent of TMP excreted in urine. Conclusions. Modification of surface morphology without significantly altering the polymorphic state can be utilized for improving physical stability of TMP suspensions. However, the pharmacokinetic profile remains unaltered.
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  • 96
    ISSN: 1573-904X
    Keywords: submicron lipid emulsion ; supersaturation ; tirilazad ; venous irritation ; pharmacokinetics ; tissue distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To compare the venous irritation, pharmacokinetics, and tissue distribution of tirilazad in rats after intravenous administration of a submicron lipid emulsion with that of an aqueous solution. Methods. Venous irritation was determined by microscopic evaluation of injury to the lateral tail veins of rats. Pharmacokinetic parameters were determined by following plasma concentrations of drug. Tissue distribution of [14C]-tirilazad was determined by quantitative whole body autoradiography. Results. Single dose injections of tirilazad as an emulsion at doses ranging from 1.52 mg to 13.5 mg were non-irritating whereas the solution was irritating at a dose of 1.3 mg. The pharmacokinetic parameters were not statistically different between the emulsion and the solution (p 〉 0.2) at doses of 6 mg/kg/day and 20 mg/kg/day. However, at 65 mg/kg/day dose, a higher AUC(0,6) (4-fold) and lower Vss (18-fold) and CL(5-fold) were observed for the lipid emulsion as compared to the solution (p 〈 0.05). Tissue distribution showed higher initial concentrations (two fold or more) in most tissues for the solution. These values, however, equilibrated by 4 h and AUC(0,4) differences were less than two fold in most tissues. Conclusions. Formulating tirilazad in the lipid emulsion significantly reduces the venous irritation without changing the pharmacokinetics and tissue distribution at low doses.
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  • 97
    ISSN: 1573-904X
    Keywords: bioequivalence ; neural networks ; prediction ; pharmacokinetics ; verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The methodology of predicting the pharmacokinetic parameters (AUC, cmax, tmax) and the assessment of their variability in bioequivalence studies has been developed with the use of artificial neural networks. Methods. The data sets included results of 3 distinct bioequivalence studies of oral verapamil products, involving a total of 98 subjects and 312 drug applications. The modeling process involved building feedforward/backpropagation neural networks. Models for pharmacokinetic parameter prediction were also used for the assessment of their variability and for detecting the most influential variables for selected pharmacokinetic parameters. Variables of input neurons based on logistic parameters of the bioequivalence study, clinical-biochemical parameters, and the physical examination of individuals. Results. The average absolute prediction errors of the neural networks for AUC, cmax, and tmax prediction were: 30.54%, 39.56% and 30.74%, respectively. A sensitivity analysis demonstrated that for verapamil the three most influential variables assigned to input neurons were: total protein concentration, aspartate aminotransferase (AST) levels, and heart-rate for AUC, AST levels, total proteins and alanine aminotransferase (ALT) levels, for cmax, and the presence of food, blood pressure, and body-frame for tmax. Conclusions. The developed methodology could supply inclusion or exclusion criteria for subjects to be included in bioequivalence studies.
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  • 98
    ISSN: 1573-904X
    Keywords: WHI-P180 ; pharmacokinetics ; quinazolines ; mast cell inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of the present study was to examine the pharma-codynamic and pharmacokinetic features of the novel mast cell inhibitor 4-(3′-Hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P180) in mice. Methods. A high performance liquid chromatography (HPLC)-based quantitative detection method was used to measure plasma WHI-P180 levels in mice. The plasma concentration-time data was fit to a single compartment pharmacokinetic model by using the WinNonlin program to calculate the pharmacokinetic parameters. A cutaneous anaphylaxis model was used to examine the pharmacodynamic effects of WHI-P180 on anaphylaxis-associated vascular hyperpermeability. Results. The elimination half-life of WHI-P180 in CD-1 mice (BALB/ c mice) following i.v., i.p., or p.o. administration was less than 10 min. Systemic clearance of WHI-P180 was 6742 mL/h/kg in CD-1 mice and 8188 mL/h/kg in BALB/c mice. Notably, WHI-P180, when administered in two consecutive nontoxic i.p. bolus doses of 25 mg/kg, inhibited IgE/antigen-induced vascular hyperpermeability in a well-characterized murine model of passive cutaneous anaphylaxis. Conclusions. WHI-P180 is an active inhibitor of IgE-mediated mast cell responses in vitro and in vivo. Further preclinical characterization of WHI-P180 may improve the efficacy of WHI-P180 in vivo and provide the basis for design of effective treatment and prevention programs for mast cell mediated allergic reactions.
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  • 99
    ISSN: 1573-904X
    Keywords: etomidate ; pharmacokinetics ; pharmacodynamics ; rat ; electroencephalogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: 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.
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  • 100
    ISSN: 1573-904X
    Keywords: antisense phosphorothioate oligonucleotide ; stealth liposome ; pharmacokinetics ; monkey ; capillary gel electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated). Methods. Encapsulated or unencapsulated ISIS 2503 was administered to rhesus monkeys by intravenous infusion. The concentrations of ISIS 2503 and metabolites in blood, plasma, and tissue samples were determined by capillary gel electrophoresis. Results. Plasma concentrations of encapsulated ISIS 2503 decreased mono-exponentially after infusion with a mean half-life of 57.8 hours. In contrast, the concentration of unencapsulated ISIS 2503 in plasma decreased rapidly with a mean half-life of 1.07 hours. Both encapsulated and unencapsulated ISIS 2503 distributed widely into tissues. Encapsulated ISIS 2503 distributed primarily to the reticulo-endothelial system and there were few metabolites observed. In contrast, unencapsulated ISIS 2503 distributed rapidly to tissue with highest concentration seen in kidney and liver. Nuclease-mediated metabolism was extensive for unencapsulated oligonucleotide in plasma and tissues. Conclusions. The data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.
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