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  • 1
    Electronic Resource
    Electronic Resource
    Effects of nonhost and host plants on insect herbivory covarying with plant size in the cruciferous plant Turritis glabra (2000)
    Springer
    Population ecology 42 (2000), S. 145-152 
    Details
    ISSN: 1437-5613
    Keywords: Key words Herbivory ; Plant–herbivore interaction ; Lepidoptera ; Cruciferous plants ; Vegetation texture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Correlation between plant size and reproductive output may be modified by herbivory in accordance with host plant density and the presence of nonhost plants. To elucidate the effects of nonhost plant density and host plant density on the intensity of herbivory and reproductive output of the host plant in relation to plant size under natural conditions, we investigated the abundance of three lepidopteran insects, Plutella maculipennis, Anthocharis scolymus, and Pieris rapae the intensity of herbivory, and fruit set of their host plant, Turritis glabra (Cruciferae). To elucidate the effects of nonhost and host plant density, we selected four categories of plots under natural conditions: low density of nonhost and high density of host plants; low density of both nonhost and host plants; high density of both nonhost and host plants; and high density of nonhost and low density of host plants. The plant size indicated by stem diameter was a good predictor of the abundance of all herbivorous species. The effects of density of nonhost and host plants on the abundance of insects varied among species and stages of insects. As the abundance of insects affected the intensity of herbivory, herbivory was more apparent on larger host plants in plots with low density of both nonhost and host plants. Consequently, the correlation between plant size and the number of fruits disappeared in low plots with density of both nonhost and host plants. In this T. glabra– herbivorous insect system, the density of nonhost plants and host plants plays an important role in modifying the relationship between plants and herbivores under natural conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00011993
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration (2000)
    Springer
    Bulletin of experimental biology and medicine 129 (2000), S. 359-361 
    Details
    ISSN: 1573-8221
    Keywords: acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02439270
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  • 3
    Electronic Resource
    Electronic Resource
    Patterns in the structure of grassland butterfly communities along a gradient of human disturbance: further analysis based on the generalist/specialist concept (2000)
    Springer
    Population ecology 42 (2000), S. 135-144 
    Details
    ISSN: 1437-5613
    Keywords: Key words Community patterns ; Lepidoptera ; Route order ; Species richness ; Species distribution ; Environmental disturbance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Kitahara and Fujii, in 1994, analyzed the butterfly communities along a gradient of human disturbance by applying the generalist/specialist concept. Butterfly species were classified into generalist or specialist species based on their voltinism (seasonal time dimension) and potential larval resource breadth (food dimension). The community structure and species composition showed the systematic changes along the gradient. To verify the generality of those trends, we monitored five grassland butterfly communities with varying degrees of human disturbance twice a month during 1985 by the line transect method at the foot of Mt. Fuji, central Japan, and analyzed their structure in a manner similar to that employed by Kitahara and Fujii. Most results were consistent with the patterns recognized by Kitahara and Fujii. The route (community) order based on increasing human disturbance was strongly and negatively correlated with butterfly species richness but with neither butterfly species diversity (H′) nor evenness (J′). Also, the degree of human disturbance was significantly and negatively correlated with the number of specialist species, but not with that of generalists, in a community. Butterfly species richness was more strongly correlated with the number of specialist species than with that of generalists. Our analyses also showed that the generalist species were distributed more widely over the communities than were the specialists. However, in contrast to the trend revealed by Kitahara and Fujii, there was no significant difference in the population densities and in the spatial population variability between the two species groups. As a whole, our analyses confirmed the consistency of most community patterns detected by Kitahara and Fujii. The causes of the inconsistencies in some patterns were thought to be mainly the present habitat conditions with a relatively short growing season at high altitudes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00011992
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  • 4
    Electronic Resource
    Electronic Resource
    Absorption and Disposition of a Selective Aldosterone Receptor Antagonist, Eplerenone, in the Dog (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1426-1431 
    Details
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007597713530
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  • 5
    Electronic Resource
    Electronic Resource
    Allometric Pharmacokinetic Scaling: Towards the Prediction of Human Oral Pharmacokinetics (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 410-418 
    Details
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007520818956
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  • 6
    Electronic Resource
    Electronic Resource
    Physiological Modeling of Altered Pharmacokinetics of a Novel Anticancer Drug, UCN-01 (7-Hydroxystaurosporine), Caused by Slow Dissociation of UCN-01 from Human α1-Acid Glycoprotein (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 553-564 
    Details
    ISSN: 1573-904X
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007512832006
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  • 7
    Electronic Resource
    Electronic Resource
    Evaluation of Using Dog as an Animal Model to Study the Fraction of Oral Dose Absorbed of 43 Drugs in Humans (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 135-140 
    Details
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007552927404
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  • 8
    Electronic Resource
    Electronic Resource
    An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    Details
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007500910566
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and Antitumor Effect of Doxorubicin Carried by Stealth and Remote Loading Proliposome (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 782-787 
    Details
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007543805947
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  • 10
    Electronic Resource
    Electronic Resource
    Potential Role of P-Glycoprotein in Affecting Hepatic Metabolism of Drugs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 903-905 
    Details
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007570517183
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  • 11
    Electronic Resource
    Electronic Resource
    Confidence Interval Criteria for Assessment of Dose Proportionality (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1278-1283 
    Details
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026451721686
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  • 12
    Electronic Resource
    Electronic Resource
    A Human Physiologically-Based Model for Glycyrrhzic Acid, A Compound Subject to Presystemic Metabolism and Enterohepatic Cycling (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1516-1525 
    Details
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007661209921
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  • 13
    Electronic Resource
    Electronic Resource
    Influence of Stereoselective Pharmacokinetics in the Development and Predictability of an IVIVC for the Enantiomers of Metoprolol Tartrate (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1019-1025 
    Details
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007595725360
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  • 14
    Electronic Resource
    Electronic Resource
    In Vivo Specific Binding Characteristics and Pharmacokinetics of a 1,4-Dihydropyridine Calcium Channel Antagonist in the Senescent Mouse Brain (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 844-850 
    Details
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007512426420
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetic-Pharmacodynamic Modelling of Morphine Transport Across the Blood-Brain Barrier as a Cause of the Antinociceptive Effect Delay in Rats—A Microdialysis Study (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1220-1227 
    Details
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026414713509
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  • 16
    Electronic Resource
    Electronic Resource
    Biodistribution of Amphotericin B When Delivered Through Cholesterol Hemisuccinate Vesicles in Normal and A. Fumigatus Infected Mice (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1236-1242 
    Details
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
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    URL: http://dx.doi.org/10.1023/A:1026418814417
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    Safety, Toxicokinetics and Tissue Distribution of Long-Term Intravenous Liposomal Amphotericin B (ambisome®): A 91-day Study in Rats (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1494-1502 
    Details
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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    URL: http://dx.doi.org/10.1023/A:1007605024942
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    New Insights into the Pharmacokinetics and Metabolism of (R,S)-Ifosfamide in Cancer Patients Using a Population Pharmacokinetic-Metabolism Model (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 645-652 
    Details
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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    URL: http://dx.doi.org/10.1023/A:1007561727948
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    Egg loads and egg masses: Parasitism ofChoristoneura rosaceana eggs by Trichogramma minutum after inundativerelease in a commercial blueberry field (2000)
    Springer
    BioControl 45 (2000), S. 257-268 
    Details
    ISSN: 1573-8248
    Keywords: biological control ; blueberry ; egg parasitoid ; inundative release ; leafroller ; Lepidoptera ; Tortricidae ; Hymenoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Inundative releases of Trichogramma minutum Riley were made in a commercialblueberry field in British Columbia, Canada, todetermine the extent of dispersal of adult wasps, andto determine whether complete parasitism of eggswithin egg masses of the target host [oblique-bandedleafroller (OBLR), Choristoneura rosaceana(Harris)] occurred. Three weekly releases of waspswere made from a single release point in the center ofeach field during the flight of first generation OBLRadults. Sticky trap, sentinel egg mass andtarget-host egg mass data all indicated only a limitedrange of dispersal of T. minutum within thefield. In addition, only partial parasitism of eggmasses of the target host occurred even in closeproximity to the release point. We discuss theimportance of determining the response of Trichogramma females to previously-parasitized eggswhen using Trichogramma wasps for biologicalcontrol of lepidopterous species that oviposit largeegg masses.
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    URL: http://dx.doi.org/10.1023/A:1009922101934
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    Predation by the hoopoe (Upupa epops) on pupae of Thaumetopoea pityocampa and the likelyinfluence on other natural enemies (2000)
    Springer
    BioControl 45 (2000), S. 311-323 
    Details
    ISSN: 1573-8248
    Keywords: bird predation ; forest ; interference ; Italy ; Lepidoptera ; pine processionary caterpillar ; parasitism,/kwd〉 ; Pinus ; Thaumetopoeidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The hoopoe (Upupa epops L.) is an insectivorousbird often preying on larvae and pupae of the pineprocessionary caterpillar (Thaumetopoeapityocampa Denis & Schiffermüller), the mostimportant defoliator of pines in Southern Europe andNorthern Africa. The first half of the breeding seasonof this migratory bird coincides with the pupal stageof the insect. Bird predation of pupae was quantifiedin two years in a Pinus nigra stand of northernItaly by periodic counting of the empty cocoons lefton the soil surface after extraction. The predationrate, estimated on 20 pupation sites representing thewhole stand, was 74.1% in 1993 and 68.3% in 1994.Predation was higher in the upper part of the soil andthen progressively decreased with increasing depth.The hoopoe may also prey on cocoons containing pupaeinfected by pathogenic fungi or parasitoids. Anexclosure experiment showed that the bird mayinterfere with these other mortality factors. Threepupal parasitoids, the ichneumonids Erigorgusfemorator Aubert and Coelichneumon rudis (Boyerde Fonscolombe) and the pteromalid Conomoriumpityocampae Graham, were significantly less frequentin the exposed sites. The fungus Beauveriabassiana (Balsamo) Vuillemin and the most abundantpupal parasitoid, Villa brunnea Becker (Diptera:Bombyliidae), caused the highest pupal mortality atboth protected and exposed sites. The bird seems to bean incompletely additive mortality factor acting onthe pest and it can also alter the relativemortalities imposed by the other natural enemies.
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    URL: http://dx.doi.org/10.1023/A:1009992321465
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    Thermal ecology of gregarious and solitary nettle-feeding nymphalid butterfly larvae (2000)
    Springer
    Oecologia 122 (2000), S. 1-10 
    Details
    ISSN: 1432-1939
    Keywords: Key words Distribution ; Gregariousness ; Larval strategy ; Lepidoptera ; Thermoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Group-living in animal populations has many possible ecological and evolutionary explanations, including predator evasion and feeding facilitation. In insects, the thermal balance of solitary and gregarious larvae is likely to differ and may thus have important ecological consequences. The abilities of the larvae of four species of nettle-feeding nymphalid butterflies to thermoregulate were quantified in the field. Larval surface body temperatures of the gregarious Aglais urticae (small tortoiseshell) and Inachis io (peacock) and the solitary Polygonia c-album (comma) and Vanessa atalanta (red admiral) were measured for each instar, in both sunny and overcast conditions, over a seasonal range of temperatures. The results suggested two distinct larval thermal strategies. In the presence of direct sunlight, the exposed gregarious larvae of A. urticae and I. io regulated body temperatures at 32.5 and 31.5°C, respectively, while the temperatures of concealed larvae of P. c-album and V. atalanta were largely dependent on ambient temperatures. In the sun, the range of body temperatures recorded for A. urticae and I. io larvae was fairly narrow relative to ambient temperatures. This suggests a high degree of thermal control in these species. Modal body temperatures coincided with the temperature at which development rate is maximal. Regardless of whether changes in thermoregulation are a cause or consequence of the evolution of gregariousness, the combination of behavioural thermoregulation and gregariousness in larval insects has important implications for voltinism patterns and range extension (via increased development rates). Distributional responses of gregarious and solitary larvae to climatic warming may differ as a result of changes in cloud cover as well as changes in temperature.
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    URL: http://dx.doi.org/10.1007/PL00008825
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    Mating opportunity and the evolution of sex-specific mortality rates in a butterfly (2000)
    Springer
    Oecologia 122 (2000), S. 36-43 
    Details
    ISSN: 1432-1939
    Keywords: Key words Life history theory ; Longevity ; Ageing ; Mortality rate ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Life history theory predicts that organisms should only invest resources into intrinsic components of life span to the degree that it pays off in terms of reproductive success. Here, we investigate if the temporal distribution of mating opportunities may have influenced the evolution of intrinsic mortality rates in the butterfly Pararge aegeria (Satyrinae). In this species, females mate only once and the frequency of male mating opportunities depends on the temporal emergence pattern of virgin females. As expected, in a population from Madeira where females emerge continuously throughout the year, there was no sex difference in adult life span, while in a Swedish population with synchronised female emergence, males had significantly shorter life spans compared to females. A logistic mortality model provided the best fit to the observed change in age-specific mortality and all categories reached an asymptotic mortality rate of a similar magnitude. However, the Swedish males reached this mortality plateau more rapidly than the other categories. External mortality, due to water and food limitation, affected the pattern of sex-specific mortality but males from Sweden still had higher rates of mortality compared to all other categories. We argue that selection on male longevity is likely to be weaker in Sweden because under synchronised emergence, all females emerge and mate within a short period of time, after which male reproductive value will quickly approach zero. On Madeira, however, male reproductive value decrease more slowly with age since the probability of finding a receptive female is constant over the year.
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    URL: http://dx.doi.org/10.1007/PL00008833
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    A comparison of the developmental and reproductive biology of two soybean pod borers, Etiella spp. in Indonesia (2000)
    Springer
    Entomologia experimentalis et applicata 97 (2000), S. 137-147 
    Details
    ISSN: 1570-7458
    Keywords: Etiella zinckenella ; Etiella hobsoni ; Lepidoptera ; Pyralidae ; soybean ; development ; reproduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments conducted in West Java, Indonesia investigated the developmental biology and reproductive behavior of two sympatric soybean pod borers, Etiella zinckenella Treitschke and E. hobsoni Butler (Lepidoptera: Pyralidae). It was determined that: (1) significant interspecific differences occurred between the egg, larval, pupal and total egg-to-adult developmental periods of laboratory raised E. zinckenella and E. hobsoni; (2) the pre-pupal and total egg-to-adult development periods of female E. zinckenella were significantly shorter than for males; (3) the longevity of virgin female E. zinckenella was significantly longer than that of virgin males, or virgin male and female E. hobsoni; (4) interspecific differences occurred in the female: male sex-ratios of laboratory raised adults; (5) peak mating for both species occurred on the second night after eclosion; (6) interspecific differences occurred in the temporal distribution of calling and mating behaviors; (7) repeated mating was observed for both species at a very low frequency; (8) interspecific mating did not occur; (9) female E. zinckenella were significantly more fecund than E. hobsoni; (10) the duration in copulo of E. zinckenella was significantly longer than that of E. hobsoni; and (11) wingtraps baited with virgin females caught only conspecific males, and reduced numbers of males were captured in traps simultaneously baited with virgin females of both species. This study demonstrates distinct biological differences and reproductive isolation between the two Etiella spp.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004099706718
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    Fecundity and fertility reductions in adult leafrollers exposed to surfaces treated with the ecdysteroid agonists tebufenozide and methoxyfenozide (2000)
    Springer
    Entomologia experimentalis et applicata 94 (2000), S. 75-83 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Tortricidae ; reproduction ; tebufenozide ; methoxyfenozide ; ecdysone agonist ; Argyrotaenia velutinana ; Choristoneura rosaceana
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects on the fecundity and fertility of redbanded leafroller, Argyrotaenia velutinana (Walker), and obliquebanded leafroller,Choristoneura rosaceana (Harris), exposed as adults to surfaces treated with the ecdysone agonists tebufenozide (RH-5992) and methoxyfenozide (RH-2485) were examined. The first part of the study consisted of recently emerged moths being exposed to treated surfaces continuously throughout their lives (including mating and oviposition). Continuous exposure to tebufenozide- or methoxyfenozide-treated surfaces significantly reduced the mean number of eggs laid and the percent of eggs that hatched in both species. The second part of the study involved exposure of recently emerged virgin moths (by sex) to treated surfaces for 24 h, after which, the exposed moths were paired with a nontreated partner to mate and oviposit on nontreated surfaces. In this experiment, for A. velutinana, significant reductions in fecundity occurred only when the female was exposed to methoxyfenozide-treated surfaces. Significant reductions in A. velutinana egg fertility occurred with both male and female exposure in the methoxyfenozide treatments and only female exposure in the tebufenozide treatments. For C. rosaceana, significant reductions in fecundity occurred with both male and female exposure in the tebufenozide and methoxyfenozide treatments. Significant reductions in C. rosaceana egg fertility occurred with both male and female exposure in the tebufenozide treatments and only with female exposure in the methoxyfenozide treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003957010320
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    Sex pheromones of Phyllonorycter acerifoliella and Ph. heegerella and communication peculiarities in three species of leafmining moths (2000)
    Springer
    Entomologia experimentalis et applicata 94 (2000), S. 15-23 
    Details
    ISSN: 1570-7458
    Keywords: calling behaviour ; periodicity ; sex pheromone ; attraction inhibitor ; attraction synergist ; field tests ; Lepidoptera ; Gracillariidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Females of the leaf miner moth Phyllonorycter acerifoliella (Z.) [=Ph. sylvella (Hw.)] and Ph. heegerella (Z.) (Lepidoptera: Gracillariidae: Lithocolletinae) release their sex pheromone at the beginning of photophase. The periodicity of the `calling' behaviour of Ph. acerifoliella females was established. Three compounds from calling virgin Ph. heegerella females were collected by the Solid Phase Micro Extraction (SPME) technique and identified as (Z)-8-tetradecenyl acetate (Z8-14:OAc), tetradecyl acetate (14:OAc) and (Z)-8-tetradecenol (Z8-14:OH) in the ratio (88±3):(2±0.6):(10±5) by capillary gas chromatography and mass spectrometry. Field trapping experiments demonstrated that the first two compounds are important for the attraction of conspecific males. Z8-14:OAc was found to be attractive when tested separately, while 14:OAc acted as synergist. The attractivity of the three component blend was reduced by 10% admixture of either (E)-10-dodecenyl acetate (E10-12:OAc) or (Z)-10-tetradecenyl acetate (Z10-14:OAc). Field tests of Z10-, Z8- and E10-14:OAc, identified from Ph. acerifoliella females, demonstrated that the first two compounds were essential for the attraction of conspecific males; so both are sex pheromone components. The attractivity of the three component blend of Z10- Z8- and E10-14:OAc was reduced by 10% admixture of (E)-10-dodecenol (E10-12:OH). The following four semiochemical compounds, Z8-14:OAc, Z8-14:OH, E10-14:OAc and 14:OAc, identified from phyllonoryctid females, as well as two sex attraction antagonists for Ph. acerifoliella and Ph. heegerella males, E10-12:OAc and Z10-14:OAc, are new for the family Gracillariidae. The results of field trapping experiments revealed mechanisms ensuring the specificity of the chemocommunication systems in Ph. acerifoliella, Ph. heegerella and Ph. ulmifoliella (Hb.) moths.
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    URL: http://dx.doi.org/10.1023/A:1003920526327
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    Behavioural observations of Pieris brassicae larvae indicate multiple mechanisms of action of analogous drimane antifeedants (2000)
    Springer
    Entomologia experimentalis et applicata 95 (2000), S. 217-227 
    Details
    ISSN: 1570-7458
    Keywords: antifeedant ; drimane ; mechanism of action ; sensory response ; toxicity ; habituation ; behavioural observation ; structure-activity relationship ; Pieris brassicae ; Lepidoptera ; Pieridae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We tested 11 analogous synthetic drimane antifeedant compounds for their feeding inhibiting effects on larvae of the large white butterfly Pieris brassicae L. (Lepidoptera: Pieridae) in no-choice tests on the host plant Brassica oleracea L. Furthermore, we observed larval feeding behaviour in no-choice tests to analyze temporal effects of five drimanes. The results show that the five analogous antifeedants differentially influence feeding behaviour and locomotion activity. Warburganal and polygodial are most likely sensory mediated antifeedants. Habituation to these compounds occurs soon after the onset of the tests (i.e., within 0.5–1.5 h). Compound 5 and confertifolin are probably not direct, sensory mediated antifeedants. After 0.5–1.5 h of exposure, these compounds inhibit not only feeding, but also locomotion behaviour, indicating postingestive, toxic effects. Isodrimenin inhibits feeding from the onset of the test and is probably a sensory mediated antifeedant. No habituation occurs to this compound, indicating that isodrimenin is either a very strong antifeedant or that it additionally has postingestive, toxic effects. Topical application of the drimanes on the larval cuticle revealed feeding inhibiting effects, but these could not be related to the occurrence of postingestive feeding inhibiting effects, indicating that this method is inappropriate to show possible postingestive effects of drimanes in P. brassicae. In conclusion, the behavioural observations performed in this research indicate that analogous drimanes inhibit feeding by P. brassicae larvae through multiple mechanisms of action. The results show that, when developing a structure activity relationship (SAR) for a series of antifeedants, it is important to distinguish the mode of action which underlies inhibition of feeding.
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    URL: http://dx.doi.org/10.1023/A:1004064931302
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    Geographical variation in female sex pheromones of the rice leaffolder moth, Cnaphalocrocis medinalis: identification of pheromone components in Japan (2000)
    Springer
    Entomologia experimentalis et applicata 96 (2000), S. 103-109 
    Details
    ISSN: 1570-7458
    Keywords: Cnaphalocrocis medinalis ; rice leaffolder ; Lepidoptera ; Pyralidae ; sex pheromone ; geographical variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Sex pheromone components of the Japanese rice leaffolder moth, Cnaphalocrocis medinalis Guenée (Lepidoptera: Pyralidae) were identified from ovipositor extracts of virgin females as (Z)-11-octadecenal, (Z)-13-octadecenal, (Z)-11-octadecen-1-ol and (Z)-13-octadecen-1-ol at a ratio of 11:100:24:36 by GC-EAD, GC, GC-MS. The total amount was estimated to be ca.0.9 ng/female. Field bioassays in Kagoshima, Japan, showed that the two aldehydes are essential for male attraction and the alcohols may have a synergistic effect on the aldehydes. A rubber septum containing 0.9 mg of the four components at the natural ratio was shown to be an effective lure for monitoring this pest in Japan. The above four components are quite different from the sex pheromone components reported previously for the same species of either Philippine or Indian origin; components were shown to be (Z)-11-hexadecenyl acetate and (Z)-13-octadecenyl acetate at a ratio of 98:2 in the Philippine blend and 1:10 in the Indian blend. Furthermore, in the field tests in Japan, neither the Philippine blend nor the Indian blend showed any attractive activity, while the Japanese blend attracted significant numbers of male moths. These results suggest that there are remarkable geographical variations in the sex pheromone composition of this species or there are several distinct species using different sex pheromone blends.
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    URL: http://dx.doi.org/10.1023/A:1004019917270
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    2-Methylisoborneol disposition in three strains of catfish: absence of biotransformation (2000)
    Springer
    Fish physiology and biochemistry 23 (2000), S. 225-232 
    Details
    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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    URL: http://dx.doi.org/10.1023/A:1007834720306
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    A Computer-Controlled Video System for Real-Time Recording of Insect Flight in Three Dimensions (2000)
    Springer
    Journal of insect behavior 13 (2000), S. 881-900 
    Details
    ISSN: 1572-8889
    Keywords: three-dimensional ; flight track recording ; orientation ; pheromones ; plant volatiles ; image analysis ; real time ; Lobesia botrana ; Lepidoptera ; Tortricidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A computer-controlled video system for real-time recording of insect flight in three dimensions is described. The flight paths of moths were recorded in a flight tunnel using two CCD cameras placed adjacent to each other at angles of 45 and 135° to the flight tunnel axis and separated by a distance of 120 cm. They were connected to two 28-level gray-scale frame grabbers via two external synchronizers. The two-dimensional coordinates of the flying insect were obtained from the two cameras at 40-ms intervals and transferred to host computer for processing and monitor for real-time display. Due to speed limitation in the image acquisition hardware, construction of the three-dimensional file was carried off-line. The flying insect was rendered as a dark spot in a bright background using a homogeneous light source. As the insect enters into the field of view of the two cameras, the light distribution changes, and the frame grabber detects only those variation in the light distribution which results from a flying insect. The target insect can be as small as 3 pixels and can be tracked in a stereoscopic field of view 60 cm long and 50 cm high. A method was developed that allowed for scalar scoring of various pheromone sources to assess their attractiveness using vector flight parameters. This method was applied successfully for optimization of pheromone blend of the grapevine moth, Lobesia botrana.
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    URL: http://dx.doi.org/10.1023/A:1007866602219
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    Bias in Butterfly Distribution Maps: The Influence of Hot Spots and Recorder's Home Range (2000)
    Springer
    Journal of insect conservation 4 (2000), S. 73-77 
    Details
    ISSN: 1572-9753
    Keywords: mapping ; database ; bias recording ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Abstract We use data from the Mersey Valley zone (3×2 km area; N = 600 I ha squares) of the Greater Manchester butterfly atlas to investigate whether recorder visits are biased by access (viz. distance from recorder's home base) and by the locations of potential hot spots. In a multiple regression analysis, visits were found to correlate significantly both with distance from home base of the recorder and with the mean and maximum number of species found in squares. Sites close to the home base of the recorder were visited more frequently than those further afield and squares with more species were visited more frequently than those squares with fewer species. Visits were also made significantly more frequently to squares with greater numbers of butterfly resources (e.g. hostplants, nectar). Furthermore, recording is biased to and away from distinct land uses, which vary significantly in species richness. Reasons are given why these biases are to be expected at all scales. The message is that future distribution mapping should be based on rigorous sampling approaches.
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    Survival and Development of Tobacco Hornworm Larvae on Tobacco Plants Grown Under Elevated Levels of Ozone (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 1-19 
    Details
    ISSN: 1573-1561
    Keywords: Insecta ; tobacco hornworm ; Manduca sexta ; tobacco ; Nicotiana tabacum ; ozone ; weather fleck ; Lepidoptera ; Sphingidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Tobacco plants, Nicotiana tabacum were grown under different levels of ozone (O3) in open-top chambers. Ozone concentrations were established by charcoal filtration, which reduced O3 to approximately one-half ambient, or by the addition of O3 to unfiltered air to increase concentrations to approximately 1.4 or 1.7 times ambient O3. Survival of tobacco hornworm, Manduca sexta, larvae was increased when second instars were fed tobacco leaves grown in chambers with elevated levels of O3. Second instars also gained significantly more weight when they were fed for one week on plants exposed to elevated levels of O3 than when they were fed plants grown in charcoal-filtered air. Ozone-treated tobacco plants had higher levels of total nitrogen (primarily reduced nitrogen) and soluble carbohydrates (sugars), and lower levels of leaf-surface components, starch, nicotine, and rutin. Increased survival and growth response of hornworm larvae to elevated O3 levels in these experiments suggests that similar responses could occur in the southeastern US tobacco production areas where O3 levels can be high enough to injure tobacco plants.
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    Field Trapping of Tomato Moth, Tuta absoluta with Pheromone Traps (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 875-881 
    Details
    ISSN: 1573-1561
    Keywords: Field trapping ; pheromone ; Lepidoptera ; Gelechiidae ; Tuta absoluta ; South American tomato moth ; Scrobipalpuloides absoluta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Field evaluations demonstrate that the addition of the minor pheromone component (3E,8Z)-tetradecadien-1-yl acetate to the major component (3E,8Z,11Z)-tetradecatrien-1-yl acetate does not significantly increase the trap catches of Tuta absoluta males in the field. The triene acetate itself is highly attractive, catching about 869 ± 255 males per trap in three consecutive nights. The addition of two isomers of the minor component (3E,8Z)-tetradecadien-1-yl acetate, (3E,11Z)-tetradecadienyl-yl acetate and (8Z,11Z)-tetradecadien-1-yl acetate, to the major component (3E,8Z,11Z)-tetradecatrien-1-yl acetate also did not significantly alter the number of the males caught in the traps.
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    Aggressive Chemical Mimicry by the Bolas Spider Mastophora hutchinsoni: Identification and Quantification of a Major Prey's Sex Pheromone Components in the Spider's Volatile Emissions (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 1235-1243 
    Details
    ISSN: 1573-1561
    Keywords: Insect pheromones ; pheromone emission ; aggressive chemical mimicry ; predation ; allomone ; Araneae ; Araneidae ; Lepidoptera ; Noctuidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The adult female bolas spider Mastophora hutchinsoni feeds exclusively on attracted males of a few moth species. This exclusivity and the behavior of the approaching moths suggest that the spider aggressively mimics the sex pheromones of its prey species. Males of the bristly cutworm, Lacinipolia renigera, are a major prey of this spider, accounting for about two thirds of the biomass of prey consumed. Female bristly cutworms produce a pheromone blend consisting of (Z)-9-tetradecenyl acetate (Z9–14 : Ac) and (Z,E)-9,12-tetradecenyl acetate (ZE-9,12–14 : Ac). To determine if M. hutchinsoni females mimic the sex pheromone components and blend ratio of L. renigera, we collected volatiles from hunting adult female spiders and analyzed them with gas chromatography–electroantennographic detection (GC-EAD) and gas chromatography–mass spectrometry (GC-MS). GC-EAD analysis of volatile collections, using a male bristly cutworm antenna as the detector and two capillary columns of different polarities, revealed the presence of peaks with retention times (R ts) identical to Z9–14 : Ac and ZE-9,12– 14 : Ac. The mass spectrum of a peak with R t of Z9–14 : Ac was identical to the mass spectrum of the synthetic equivalent. There was an insufficient quantity of the compound with R t of ZE-9,12–14 : Ac to get a full spectrum, but selective detection of ions at m/z 61 and 192 at the correct R t supported the identification. On average, the blend collected from spiders contained 54.8 ± 20.8 (SE) pg/min of Z9–14 : Ac and 2.5 ± 1.7 (SE) pg/min of ZE-9,12–14 : Ac. The latter, on average, comprised 2.6 ± 0.7% of the total, which is similar to the blend ratio emitted by bristly cutworm females. Our results indicate that the adult female M. hutchinsoni produces an allomone blend that mimics not only the composition, but also the blend ratio, of the sex pheromone of a major prey species.
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    Identification of Chiral Sex Pheromone Secreted by Giant Geometrid Moth, Biston robustum Butler (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 2579-2590 
    Details
    ISSN: 1573-1561
    Keywords: Female sex pheromones ; Lepidoptera ; Geometridae ; Ennominae ; epoxynonadecene ; epoxynonadecadiene ; chiral epoxide ; chiral HPLC ; dimethyl disulfide adduct
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Biston robustum Butler, a polyphagous defoliator, multiplied on Hachijo-jima Island in 1997–1998. Based on GC-MS data of authentic standards, an analysis of a pheromone gland extract of the females indicated that it included (Z,Z)-6,9–nonadecadiene (I), (Z,Z,Z)-3,6,9–nonadecatriene (II), cis-(Z)-6,7–epoxy-9–nonadecene (III), and cis-(Z,Z)-6,7–epoxy-3,9–nonadecadiene (IV) in a ratio of 13 : 2 : 70 : 15. The structure of III was confirmed by a GC-MS analysis of another extract treated with dimethyl disulfide (DMDS). This epoxymonoene was successfully converted into the corresponding DMDS adduct that showed diagnostic ions fragmented at an epoxy ring and at thiomethoxy groups reflecting the position of an original double bond. Furthermore, the 6S,7R configuration was assigned for the epoxy ring of III by chiral HPLC analysis. Field examination of synthetic lures revealed that the two epoxy compounds (III and IV) with the 6S,7R configuration were essential components and that the two unsaturated hydrocarbons (I and II) showed a synergistic effect on male attraction.
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    Decadienoates: Sex Pheromone Components of Nettle Caterpillars Darna trima and D. bradleyi (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 1969-1981 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Limacodidae ; Darna trima ; Darna bradleyi ; Setothosea asigna ; Setora nitens ; nettle caterpillars ; oil palm ; sex pheromone ; 2-methylbutyl (E)-7,9-decadienoate ; (E)-2-hexenyl (E)-7,9-decadienoate ; methyl (E)-7,9-decadienoate ; isobutyl (E)-7,9-decadienoate ; (E)-9dodecenal ; (E)-9,11-dodecadienal ; (Z)-9-dodecenal ; (Z)-9,11-dodecadienal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract This study was undertaken to identify sex pheromone components of nettle caterpillars Darna trima and Darna bradleyi (Lepidoptera: Limacodidae) whose larvae defoliate oil palm, Elaeis guineensis, in southeast Asia. Coupled gas chromatographic–electroantennographic detection (GCEAD) analyses of pheromone gland extracts revealed two antennally active compounds produced by female D. trima and two by female D. bradleyi. Molecular structures of these candidate pheromone components were identified by electron-impact and chemical-ionization mass spectrometry; retention-index calculations on DB-5, DB-23, and DB-210 columns; microanalytical treatments, as well as syntheses of "auxilliary" compounds that facilitated identification of the compounds. The compounds from D. trima were 2-methylbutyl (E)-7,9-decadienoate (A) and (E)-2-hexenyl (E)-7,9decadienoate (B); from D. bradleyi we identified methyl (E)-7,9-decadienoate (C), and isobutyl (E)-7,9-decadienoate (D). In field experiments in Malaysia, (S)-2-methylbutyl (E)-7,9-decadienoate (SA) in combination with B proved to be essential and synergistic pheromone components for attraction of male D. trima. (R)-2-Methylbutyl (E)-7,9-decadienoate (RA) had no behavioral activity. Compound D singly attracted male D. bradleyi, but addition of C to D at a 1 : 10 ratio significantly enhanced attractiveness of the bait. Synthetic pheromone blends were more effective trap baits than unmated female moths and could be developed for monitoring populations of D. trima and D. bradleyi in Asian oil palm plantations.
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    Sex Pheromone Components of Nettle Caterpillar, Setora nitens (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 1983-1990 
    Details
    ISSN: 1573-1561
    Keywords: Setora nitens ; Setothosea asigna ; nettle caterpillar ; Limacodidae ; Lepidoptera ; sex pheromone ; (Z)-9-dodecenal ; (Z)-9,11-dodecadienal ; (E)-9-dodecenal ; (E)-9,11-dodecadienal ; oil palm ; Elaeis guineensis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Gas chromatographic–electroantennographic detection (GC-EAD) analyses of pheromone gland extracts of female nettle caterpillars, Setora nitens, revealed four compounds that consistently elicited responses from male moth antennae. Retention indices on three fused silia columns (DB-5, DB-23, and DB-210) of two EAD-active compounds were almost identical to those of (E)-9-dodecenal (E9–12 : Ald) and (E)-9,11-dodecadienal (E9,11–12 : Ald), two pheromone components previously identified in congeneric Setothosea asigna. However, comparative GC, GC-EAD, and GC-mass spectrometry of extracted S. nitens compounds and authentic standards revealed that the candidate pheromone components were (Z)-9-dodecenal (Z9–12 : Ald) and (Z)-9,11-dodecadienal (Z9,11–12 : Ald). The two other EAD-active compounds in pheromone gland extracts proved to be the corresponding alcohols to these aldehydes. In field-trapping experiments in Tawau, Malaysia, synthetic Z9–12 : Ald and Z9,11–12 : Ald at a 1 : 1 ratio, but not singly, attracted male S. nitens. Attractiveness of these two aldehydes could not be enhanced through the addition of their corresponding alcohols. Whether these differences in pheromone biology and chemistry between S. nitens and S. asigna are sufficient to prevent cross-attraction of heterospecific males or whether nonpheromonal mechanisms are required to maintain reproductive isolation is currently being studied.
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    Identification of a Sex Pheromone Component of the Raspberry Budmoth, Heterocrossa rubophaga (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 2549-2555 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Carposinidae ; (Z)-12–nonadecen-9–one ; chemical identification ; trapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The female-produced sex pheromone of the New Zealand raspberry budmoth, Heterocrossa rubophaga, was investigated. Gas chromatographic–mass spectrometric analyses revealed the ketone, (Z)-12–nonadecen9–one (Z12–19–9–one). This compound had previously been found in extracts of the sex pheromone gland of the only other carposine moth for which a sex pheromone has been identified, Carposina niponensis, although its effect on the behavior of C. niponensis males had not been established. Field trapping trials in berry fruit gardens showed this compound to elicit high catches of male H. rubophaga, with the catch appearing to plateau (and perhaps decrease) above a dosage of 300 μg on a red rubber septum. In an analysis of an extract of female H. rubophaga sex pheromone glands, there was a suggestion that the homologous (Z)-7–eicosen-11–one, the known sex pheromone component of C. niponensis, was also present. However this could not be established unequivocally and, in a field trial, addition of a small amount of this compound to Z12–19–9–one resulted in no significant increase in trap catch relative to traps baited with Z12–19–9–one alone.
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    1-Methylethyl Octanoate, a New Lepidopteran Sex Pheromone from the Bagworm, Megalophanes viciella (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 487-495 
    Details
    ISSN: 1573-1561
    Keywords: Megalophanes viciella ; Psychidae ; Lepidoptera ; bagworm ; sex pheromone ; 1-methylethyl octanoate ; 2-propyl octanoate ; field tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Extracts obtained by rinsing the thorax and extracts from the tergal sex pheromone gland of females of the bagworm moth, Megalophanes viciella, as well as headspace samples from live animals, were analyzed to reveal the chemical structure of the pheromone. As a result, 1-methylethyl octanoate was established as a main sex pheromone component of this species. This was further confirmed by numerous catches of conspecific males in traps baited with this compound in Bulgaria and Roumania.
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    Cherry Bark Tortrix, Enarmonia formosana: Olfactory Recognition of and Behavioral Deterrence by Nonhost Angio- and Gymnosperm Volatiles (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 809-821 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Tortricidae ; Enarmonia formosana ; cherry bark tortrix ; kairomone ; host selection ; foraging behavior ; plant volatiles ; nonhost volatiles ; repellency/inhibition ; oviposition deterrence ; hexanol ; benzyl alcohol ; nonanal ; decanal ; α-pinene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We tested the hypothesis that males and females of the cherry bark tortrix (CBT), Enarmonia formosana, antennally perceive and behaviorally respond to volatiles from nonhost plants. Volatiles from flowering cherry trees, Prunus serrulata Kwanzan, and from nonhost trees, including trembling aspen, Populus tremuloides, grand fir, Abies grandis, Norway spruce, Picea abies, and Scots pine, Pinus sylvestris, were captured on Porapak Q and extracts analyzed by coupled gas chromatographic–electroantennographic detection (GC-EAD). Compounds that elicited responses from male and female antennae were identified by coupled GC–mass spectrometry (MS) and by comparative GC-MS and GC-EAD with authentic standards. In field cage and field experiments, nonanal from aspen trees and (±)-α-pinene from coniferous trees were effective in reducing captures of male CBT in pheromone-baited traps and deterring oviposition by female CBT on cherry blocks. Recognition of nonhost volatiles, such as nonanal and α-pinene, may allow male and/or female CBT to avoid trees that provide inadequate concealment from predators during calling, resting, and copulation and that are unsuitable for oviposition and development of offspring. Nonhost volatiles may also be exploited for control of CBT by disrupting both mate- and host-finding.
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    Major Sex Pheromone Component of Female Herald Moth Scoliopteryx libatrix is the Novel Branched Alkene (6Z,13)-Methylheneicosene (2000)
    Springer
    Journal of chemical ecology 26 (2000), S. 1135-1149 
    Details
    ISSN: 1573-1561
    Keywords: Scoliopteryx libatrix ; Noctuidae ; Lepidoptera ; sex pheromone ; methylalkene ; (6Z13)-methylheneicosene ; electroantennogram ; field test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The major component of the female-produced sex pheromone of Scoliopteryx libatrix has been characterized by chemical analysis, synthesis, electrophysiological studies and field tests as (6Z,13)-methylheneicosene, probably the 13S-isomer. This is the first example of a branched chain alkene as a sex pheromone in the Noctuidae and is markedly different from the pheromones of other members of the family. The systematic position of S. libatrix, belonging to a monotypic genus of a one-member subfamily within the Noctuidae, may reflect the unusual structure of the sex pheromone.
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    Host range and gene contents of Bacillus thuringiensis strains toxic towards Spodoptera exigua (2000)
    Springer
    Entomologia experimentalis et applicata 97 (2000), S. 339-346 
    Details
    ISSN: 1570-7458
    Keywords: crygenes ; PCR ; Lepidoptera ; Spodoptera ; insecticidal activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Thirty-five strains of the entomopathogenic bacterium Bacillus thuringiensisactive on Spodoptera exigua, were characterized by means of serological identification and determination of crygene contents by PCR. The insecticidal activity of these 35 strains was further confirmed against S. exiguaand tested against two other species of the same genus: S. littoralisand S. frugiperda. The results indicate that serovars aizawai, thuringiensis, and kurstakiwere the most frequent within S. exigua-active strains and that serovar aizawaihad the highest number of strains exhibiting toxicity against the three species bioassayed. The presence in crygenes as determined by PCR suggests a non random distribution of some crygenes among serovars. Genes cry1C, cry1D, and cry1E, which are known to code for proteins toxic against Spodopteraspecies, were very common within S. exigua-active strains, specially in those belonging to serovar aizawai. However, some strains harbouring one or more of these genes were not toxic to S. littoralisor S. frugiperda; and some strains lacking all of the Spodoptera-active genes were found to be toxic to all three species. This suggests differences in the expression levels among strains bearing toxic genes and the involvement of other genes toxic to Spodopteraspecies. Since strains sharing the same crygenes exhibited different host ranges, the results indicate the need to perform toxicity bioassays in addition to other tests (serological identification and PCR) in order to determine the insecticidal activity of B. thuringiensisstrains.
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    Pharmacology of Fluorinated Pyrimidines: Eniluracil (2000)
    Springer
    Investigational new drugs 18 (2000), S. 373-381 
    Details
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
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    Insects of the Muni-Pomadze Ramsar site (2000)
    Springer
    Biodiversity and conservation 9 (2000), S. 479-486 
    Details
    ISSN: 1572-9710
    Keywords: biodiversity ; butterfly ; Ghana ; insect ; lagoon ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A variety of collection methods were used to inventory the insect diversity of the Muni-Pomadze Ramsar site along the Ghana coastline. A total of 75 butterfly species in five families were collected and identified. Twenty-six percent of the butterfly species were open country species. The butterflies were all typical of the coastal zone and no endangered or narrowly endemic species were recorded. The Muni-Pomadze site was also rich in other insect species (67 insect species belonging to 15 orders) as a result of the diverse terrestrial habitats surrounding the lagoon. Butterfly species composition changed with habitat indicating a fine-grained response by the butterfly communities to habitat changes. Data from long-term monitoring of butterfly communities at Muni-Pomadze could prove useful as indicators of habitat quality.
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    Mechanism-Based Modeling of Functional Adaptation Upon Chronic Treatment with Midazolam (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 321-327 
    Details
    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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    Population Pharmacokinetic/ Pharmacodynamic Modeling of Cetrorelix, a Novel LH-RH Antagonist, and Testosterone in Rats and Dogs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 328-335 
    Details
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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    Bioequivalence of Methylphenidate Immediate-Release Tablets Using a Replicated Study Design to Characterize Intrasubject Variability (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 381-384 
    Details
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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    URL: http://dx.doi.org/10.1023/A:1007560500301
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    Pharmacokinetics of a Hematoregulatory Peptide (SK&F 107647) in Healthy Male Volunteers and in Patients with Colorectal or Pancreatic Adenocarcinoma Not Amenable to Standard Therapy (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 385-390 
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    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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    In Vivo Absorption Properties of Orally Administered Recombinant Human Interleukin-11 (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 482-485 
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    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007545524408
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    Effects of mating history on ejaculate size, fecundity, longevity, and copulation duration in the ant-tended lycaenid butterfly, Jalmenus evagoras (2000)
    Springer
    Behavioral ecology and sociobiology 47 (2000), S. 119-128 
    Details
    ISSN: 1432-0762
    Keywords: Key words Copulation duration ; Explosive mating system ; Ejaculate size ; Lepidoptera ; Mating history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The mating system of the Australian lycaenid butterfly, Jalmenus evagoras, is highly unusual compared to most other Lepidoptera. Characteristics of this system, which has been termed an ’explosive mating strategy,’ include the formation of an intensely competitive mating aggregation of males, a highly male biased operational sex ratio, a lack of discrimination and mate choice by both sexes, a high variance in male mating success, and female monogamy. In this study, we tested the hypothesis that multiple mating by males imposes physiological costs resulting in smaller spermatophores, and that this results in a fitness cost to females. We found that male J. evagoras transferred only 2.2% of their eclosion weight during their first mating, consistent with the hypothesis that males of monandrous species produce a relatively small investment. The wet weight of the ejaculate declined by an average of 27% at the second mating and the dry weight by 29%, and an intermating interval of 5–9 days was needed for the ejaculate to return to the size at the first mating, regardless of male size or age. Wet ejaculate mass increased proportionally with male size, though dry mass was proportionally larger in smaller males. Ejaculate mass tended to increase with male age at both first and second matings. Female characteristics, in general, did not affect ejaculate mass, although the wet weight of the ejaculate was positively associated with female weight at the second mating. Copulation duration increased from 2.4 h to approximately 3 h at the second mating, and to over 4 h at the third and fourth matings. Fecundity was positively correlated with female size but not with mating history, copulation duration, or any other characteristics measured for either males or females. Female longevity declined significantly as the number of times the male partner had previously mated increased. We conclude that despite the small male investment in ejaculate, the costs of multiple mating may nonetheless be significant, as indicated by the reduction in ejaculate mass, an increase in copulation duration, and reduction in female lifespan with increasing mating number.
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    URL: http://dx.doi.org/10.1007/s002650050002
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    Assuming Peripheral Elimination: Its Impact on the Estimation of Pharmacokinetic Parameters of Muscle Relaxants (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 491-512 
    Details
    ISSN: 1573-8744
    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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    Fine-scale resolution of closely spaced pheromone and antagonist filaments by flying male Helicoverpa zea (1999)
    Springer
    Journal of comparative physiology 185 (1999), S. 131-141 
    Details
    ISSN: 1432-1351
    Keywords: Key wordsHelicoverpa zea ; Noctuidae ; Lepidoptera ; Sex pheromone ; Antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The limits of a male moth's ability to resolve closely spaced odor filaments have been investigated. Male Helicoverpa zea normally respond to their conspecific sex pheromone blend by exhibiting an upwind flight, which culminates in source contact by at least 50% of the bioassayed individuals. When loaded onto the same filter paper source containing this hitherto attractive pheromone blend, or onto a separate filter paper and co-emitted from the same pipette source with pheromone, (Z)-11-hexadecenyl acetate severely reduced upwind flight and source contact by male H. zea. A similar level of upwind flight inhibition was recorded when the antagonist (Z)-11-hexadecenyl acetate was emitted from its own point source placed 1 mm upwind of the pheromone point source, both plumes being simultaneously emitted in a continuous mode to form a confluent strand. However, (Z)-11-hexadecenyl acetate was less effective in reducing upwind flight and source contact when it was isolated and pulsed from its own source, placed 1 mm either upwind, downwind or cross-wind of a pipette source from which pheromone was simultaneously being pulsed, such that both filaments were separated in time by 0.001–0. 003 s. These results suggest that male H. zea are able to distinguish between odor sources separated by as little as 1 mm in space and 0.001 s in time.
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    URL: http://dx.doi.org/10.1007/s003590050372
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    Trichromatic colour vision in the hummingbird hawkmoth, Macroglossum stellatarum L. (1999)
    Springer
    Journal of comparative physiology 184 (1999), S. 535-541 
    Details
    ISSN: 1432-1351
    Keywords: Key words Insects ; Lepidoptera ; Macroglossum stellatarum ; Colour vision ; Red receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Hymenopterans have long been shown to choose colours by means of the spectral distribution and independently of the intensity (true colour vision). The same ability has only very recently been proven for two butterfly species. We present evidence for the existence of true colour vision in the European hummingbird hawkmoth, Macroglossum stellatarum. Moths were trained in dual-choice situations to spectral lights of a rewarding and an unrewarding wavelength. After training, unrewarded tests were performed during which the intensities of the lights were changed. The results confirm that the species has three spectral receptor types and uses true colour vision when learning the colour of a food source. If colour vision is not possible since only one receptor type is receiving input from both stimuli, the moths learn to associate some achromatic cue correlated to the receptor quantum catch, with the reward. The moths learn spectral cues rapidly and choose correctly after one to several rewarded visits even when trained to different colours in sequence.
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    Distribution of a 20-Mer Phosphorothioate Oligonucleotide, CGP69846A (ISIS 5132), into Airway Leukocytes and Epithelial Cells Following Intratracheal Delivery to Brown-Norway Rats (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1542-1549 
    Details
    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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    Pharmacokinetic Features and Metabolism of Calphostin C, A Naturally Occurring Perylenequinone with Antileukemic Activity (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1003-1009 
    Details
    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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    Characterization of Ocular Pharmacokinetics of Beta-Blockers Using a Diffusion Model After Instillation (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1596-1601 
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    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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    A Pharmacokinetic Model for Tenidap in Normal Volunteers and Rheumatoid Arthritis Patients (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1608-1615 
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    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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    Modeling of Pharmacokinetic/Pharmacodynamic (PK/PD) Relationships: Concepts and Perspectives (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 176-185 
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    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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    Pharmacokinetics of Aminolevulinic Acid After Intravesical Administration to Dogs (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 288-295 
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    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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    Improved Lipid Lowering Activity of Bezafibrate Following Continuous Gastrointestinal Administration: Pharmacodynamic Rationale for Sustained Release Preparation of the Drug (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1093-1097 
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    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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    Pharmacokinetics of Methotrexate in the Extracellular Fluid of Brain C6-Glioma After Intravenous Infusion in Rats (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1219-1225 
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    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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    Evaluation of the Pharmacokinetic Features and Tissue Distribution of the Potent Nonnucleoside Inhibitor of HIV-1 Reverse Transcriptase, N-[2-(2-fluorophenethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (HI-240) with an Analytical HPLC Method (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1226-1232 
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    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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    Influence of Crystal Habit on Trimethoprim Suspension Formulation (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 261-265 
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    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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    URL: http://dx.doi.org/10.1023/A:1018832526093
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    Venous Irritation, Pharmacokinetics, and Tissue Distribution of Tirilazad in Rats Following Intravenous Administration of a Novel Supersaturated Submicron Lipid Emulsion (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 930-938 
    Details
    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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    Prediction of Pharmacokinetic Parameters and the Assessment of Their Variability in Bioequivalence Studies by Artificial Neural Networks (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 944-948 
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    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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    URL: http://dx.doi.org/10.1023/A:1018857108713
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    Pharmacokinetics and Biologic Activity of the Novel Mast Cell Inhibitor, 4-(3′-Hydroxyphenyl)-amino-6,7-dimethoxyquinazoline in Mice (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 117-122 
    Details
    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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    Relationship Between Etomidate Plasma Concentration and EEG Effect in the Rat (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 924-929 
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    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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    Pharmacokinetics and Tissue Disposition in Monkeys of an Antisense Oligonucleotide Inhibitor of Ha-Ras Encapsulated in Stealth Liposomes (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1309-1315 
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    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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    Safety and Toxicokinetics of Intravenous Liposomal Amphotericin B (AmBisome ®) in Beagle Dogs (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1694-1701 
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    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; tissue distribution ; toxicity ; toxicokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome ®) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses. Methods. Beagle dogs (5/sex/group) received intravenous AmBisome (0.25, 1,4, 8, and 16 mg/kg/day), empty liposomes or vehicle for 30 days. AmB was determined in plasma on days 1, 14, and 30, and in tissues on day 31. Safety parameters included body weight, clinical chemistry, hematology and microscopic pathology. Results. Seventeen of twenty animals receiving 8 and 16 mg/kg were sacrificed early due to weight loss caused by reduced food intake. Dose-dependent renal tubular nephrosis, and other effects characteristic of conventional AmB occurred at 1 mg/kg/day or higher. Although empty liposomes and AmBisome increased plasma cholesterol, no toxicities unique to AmBisome were revealed. Plasma ultrafiltrates contained no AmB. AmBisome achieved plasma levels 100-fold higher than other AmB formulations. AmBisome kinetics were non-linear, with clearance and distribution volumes decreasing with increasing dose. This, and nonlinear tissue uptake, suggest AmBisome disposition was saturable. Conclusions. AmBisome has the same toxic effects as conventional AmB, but they appear at much higher plasma exposures. AmBisome's non-linear pharmacokinetics are not associated with increased risk, as toxicity increases linearly with dosage. Dogs tolerated AmBisome with minimal to moderate changes in renal function at doses (4 mg/kg/day) producing peak plasma concentrations of 18−94 µg/mL.
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    Distribution and Binding Kinetics of Ciprofloxacin and Ofloxacin in the Hindlimb of the Rat (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 587-591 
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    ISSN: 1573-904X
    Keywords: quinolones ; pharmacokinetics ; permeability ; tissue binding ; hindlimb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1023/A:1011939616948
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    Analyzing Rich Data Using Different Methods Provided by NONMEM: Pharmacokinetics of Telmisartan Following Intravenous Infusion to Healthy Volunteers (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 772-776 
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    ISSN: 1573-904X
    Keywords: nonlinear mixed effects modeling (NONMEM) ; pharmacokinetics ; telmisartan ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1023/A:1011997229669
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    Effects of Hyperlipidemia on the Pharmacokinetics of Nifedipine in the Rat (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 309-313 
    Details
    ISSN: 1573-904X
    Keywords: hyperlipidemia ; hypercholesterolemia ; nifedipine ; pharmacokinetics ; protein binding ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The effect of hyperlipidemia on nifedipine pharmacokinetics was studied. The mechanisms by which hyperlipidemia affects pharmacokinetics of drugs are mainly undetermined. Hyperlipidemia may decrease the fraction of unbound drug in plasma and/or decrease intrinsic ability of the cytochrome P-450 systems due to excess membrane cholesterol. Hyperlipidemia is a primary risk factor for coronary artery disease leading to hypertension and ischemic heart disease, for which nifedipine, a calcium channel blocker, is used. Methods. Poloxamer 407 (P407)-induced hyperlipidemic rat model was used to study the effects of hyperlipidemia on the pharmacokinetics of nifedipine (6 mg kg−1 given iv, ip and po). Total plasma cholesterol levels increased from 0.82−2.02 to 5.27−11.05 mmol L−1 48 h post P407 administration (Ig kg−1, ip). Protein binding studies were conducted by an ultrafiltration method. Results. Hyperlipidemia significantly decreased CLTB by 38% and CLTB/F by 45 and 42% following po and ip doses, respectively, thereby increasing AUC0−∞, Cmax and half-life. Absolute bioavailability and Vdss remained unchanged. AUC0−∞ was affected to the same extent in each route of administration, therefore, the effect was mainly systemic rather than presystemic. Hyperlipidemia significantly lowered the fraction unbound in plasma by approximately 31%. Conclusions. The altered pharmacokinetics of nifedipine by P407-induced HYPERLIPIDEMIA may be, at least in part, due to the decrease in fraction unbound in plasma. A decrease in intrinsic clearance, however, cannot be ruled out.
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    Restructuring of Lepidoptera communities by introduced Vespula wasps in a New Zealand beech forest (1999)
    Springer
    Oecologia 119 (1999), S. 565-571 
    Details
    ISSN: 1432-1939
    Keywords: Key wordsVespula ; Lepidoptera ; Phenology ; Shared predator ; Ecological impact
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Introduced social wasps (Vespula vulgaris) reach high densities in some New Zealand beech forests, because honeydew provides an abundant high-energy food source. We manipulated wasp density to estimate an “ecological damage threshold” for large, free-living Lepidoptera larvae. There will be a continuum of ecological damage thresholds for wasp density depending on the prey species or habitat. Experimentally placed small caterpillars had a significantly higher survival rate than large caterpillars, and the survival rate of both groups decreased with increasing wasp density. Spring-occurring caterpillars have a probability of surviving of 0.90–0.95, assuming wasps are the only source of mortality. However, at the peak of the wasp season we predict caterpillars would have virtually no chance (probability of 10−78 to 10−40) of surviving to adults. Wasp abundance must be reduced by at least 88% to conserve the more vulnerable species of free-living caterpillars at wasp densities similar to those observed in our study sites. This equates to a damage threshold of 2.7 wasps per Malaise trap per day. It was exceeded for about 5 months of the year in non-poisoned sites. There are currently no biological or chemical control techniques available in New Zealand that will reduce wasp abundance below this damage threshold throughout the year. Our models show that most Lepidoptera with spring caterpillars will be able to persist, but species with caterpillars occurring in the peak wasp season will be eliminated.
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    Effect of plant lectins on larval development of the legume pod borer, Maruca vitrata (1999)
    Springer
    Entomologia experimentalis et applicata 93 (1999), S. 179-187 
    Details
    ISSN: 1570-7458
    Keywords: artificial diet ; insecticidal activity ; legume pod borer ; Lepidoptera ; Maruca vitrata ; plant lectins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The legume pod-borer Maruca vitrata (Fabricius), [Lepidoptera: Pyralidae] is a major constraint restricting increased cowpea production in tropical Africa and Asia. Since lectins are known to have insecticidal properties against several pests, a survey was undertaken to screen for the effects of 25 lectins from 15 plant families on the development of Maruca pod borer (MPB) larvae. The list included 8 galactose/N-acetylgalactosamine-, 7 mannose-, 5 complex glycan-, 2 sialic acid- and 3, N-acetylglucosamine-specific lectins. Feeding bioassays using artificial diet were carried out at 2% (w/w) topical levels. Although a total of 16 lectins had detrimental effects pertaining either to larval survival, weight, feeding inhibition, pupation, adult emergence and/or fecundity, only the Listera ovata agglutinin (LOA) (Orchidaceae) and Galanthus nivalis (Amaryllidaceae) agglutinin were effective against MPB larvae for all six parameters examined. Larval mortality and feeding inhibition caused by the most active lectin (LOA) was above 60%.
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    Pheromone-mediated mating disruption of Choristoneura rosaceana: is the most attractive blend really the most effective? (1999)
    Springer
    Entomologia experimentalis et applicata 90 (1999), S. 37-47 
    Details
    ISSN: 1570-7458
    Keywords: Choristoneura rosaceana ; obliquebanded leafroller ; Lepidoptera ; Tortricidae ; mating disruption ; mechanisms ; pheromone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An attractive four-component pheromone blend containing a major component Z11-tetradecenyl acetate, and three minor components, E11-tetradecenyl acetate, Z11-tetradecenyl alcohol, and Z11-tetradecenyl aldehyde was tested as a mating disruptant against western Canadian populations of the obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae), in organic apple orchards in British Columbia. Efficacy of this four-component blend was compared to that of partial pheromone blends containing the major component plus one or two minor components. A trapping experiment confirmed that, Conrel® fibre disruption dispensers containing the four-component blend were more attractive than disruption dispensers containing the two- or three-component partial blends. A small-plot protocol was followed to compare atmospheric treatments with these blends as mating disruptants at a release rate of 10 mg ha−1 h−1 and from 1000 dispensers ha−1. Mechanisms of mating disruption, such as false-trail following and camouflage of pheromone plumes, that may be evoked to a greater degree by an attractive blend, did not appear to augment the effectiveness of mechanisms invoked by the less attractive blends, as the proportion of mating among tethered females was equal in plots treated with these blends and was reduced by 85–90% compared to the nontreated control. When the four-component pheromone blend was tested at different release rates, mating disruption in small plots began to break down at a release rate of 1.3 mg ha−1 h−1 using a dispenser density of 1000 ha−1. Above 1.3 mg ha−1 h−1 there was no dose response in release rates tested and at release rates below this dose the proportion of tethered females mating was the same as in the nontreated control. The four-component pheromone blend was tested against, and found to be no more effective than, the two-component partial blend at the threshold release rate of 1.3 mg ha−1 h−1 when it was released from 1000 or 250 disruption dispensers. Our results suggest that disruption mechanisms evoked by the attractive blend did not enhance the mating disruption effect provided by the simple blend, therefore a two-component blend may be useful in an operational mating disruption program for C. rosaceana.
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    Effect of avocadofurans on larval survival, growth, and food preference of the generalist herbivore, Spodoptera exigua (1999)
    Springer
    Entomologia experimentalis et applicata 90 (1999), S. 131-140 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Noctuidae ; avocadofurans ; Spodoptera exigua ; avocado ; idioblast ; oil cell ; food preference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We examined the effect of two avocadofurans, 2-(pentadecyl)furan and 2-(heptadecyl)furan, from avocado idioblast oil cells on maturation and larval feeding behavior of a generalist insect herbivore, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae). Experiments were conducted using two larval sizes: early-stadium larvae refer to those larvae from experiments initiated with neonates while late-stadium larvae refer to those larvae from experiments initiated with third instars. In order to use selected sublethal doses for developmental and behavioral studies on early- and late-stadium larvae, log-dose probit lines were determined using diet incorporation bioassays. Both avocadofurans had similar toxicities to early-stadium larvae [LC50=2.2 and 1.9 μmoles/g of diet for 2-(pentadecyl)furan and 2-(heptadecyl)furan, respectively] and late-stadium larvae (LC50=3.0 and 3.4 μmoles/g of diet, respectively). In diet bioassays extending from egg hatch to adult emergence, the avocadofurans significantly prolonged larval developmental times and reduced S. exigua pupal weights. In 7 d no-choice bioassays initiated with cohorts of newly-molted third instars, the avocadofurans significantly reduced larval weights at various sublethal concentrations (below LC50 values). To test larval feeding deterrence effects of these avocadofurans, choice tests were conducted using early and older instar larvae. A significantly higher proportion of early-stadium larvae preferred control diet over diet treated with either avocadofuran at several sublethal concentrations. Similarly, choice tests with late-stadium larvae showed greater proportions of larvae on control diet than treated diet even at concentrations below the LC50. Moreover, late-stadium larvae consumed significantly more of the control diet than the treated diet. Thus, the avocadofurans may act as feeding deterrents as well as toxicants in plant protection against non-adapted insect herbivores.
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    Ostrinia spp. in Japan: their host plants and sex pheromones (1999)
    Springer
    Entomologia experimentalis et applicata 91 (1999), S. 237-244 
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    ISSN: 1570-7458
    Keywords: host plant range ; sex pheromone ; Ostrinia furnacalis ; Ostrinia latipennis ; Ostrinia nubilalis ; Ostrinia orientalis ; Ostrinia palustralis ; Ostrinia scapulalis ; Ostrinia zaguliaevi ; Ostrinia zealis ; Lepidoptera ; Pyralidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To contribute to the understanding of the genus Ostrinia (Lepidoptera; Pyralidae) in Japan, we collected larvae of Ostrinia spp. from known host plants and plants not recorded as hosts, and we examined the morphology and sex pheromones of the adults obtained. Consequently, the host plant ranges of the 7 Ostrinia spp. in Japan were clarified, and the sex pheromones of the 5 species O. scapulalis, O. zealis, O. zaguliaevi, O. palustralis and O. latipennis were identified in addition to that of the Asian corn borer O. furnacalis. The phylogenetic relationships of Japanese Ostrinia spp., with reference to the European corn borer O. nubilalis, are discussed based on these findings and results of molecular phylogenetic analyses.
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    Reidentification of the female sex pheromone of the Indian meal moth, Plodia interpunctella: evidence for a four-component pheromone blend (1999)
    Springer
    Entomologia experimentalis et applicata 92 (1999), S. 137-146 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Pyralidae ; Plodia interpunctella ; Indian meal moth ; pheromone components ; GC-EAD ; stored-product pest ; behaviour ; flight tunnel ; trapping ; Ephestia kuehniella
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Pheromone gland extracts from calling female Plodia interpunctella contained at least seven compounds that consistently elicited electroantennographic responses from male antennae upon gas chromatographic analysis. Three of these compounds were found to be the previously identified gland constituents, i.e., (Z,E)-9,12-tetradecadienyl acetate (Z9,E12-14:OAc), (Z,E)-9,12-tetradecadienal (Z9,E12-14:Ald) and (Z,E)-9,12-tetradecadienol (Z9,E12-14:OH). A fourth EAD-active compound was identified as (Z)-9-tetradecenyl acetate (Z9-14:OAc). The homologue (Z)-11-hexadecenyl acetate (Z11-16:OAc) was also identified in the extracts, but showed no EAD activity. The identity of all five compounds was confirmed by comparison of GC retention times and mass spectra with those of synthetic standards. In flight tunnel tests there were no significant differences in response of male P. interpunctella to the bait containing all four EAD-active compounds and the responses to female gland extacts. A behavioural assay of different two-compound blends in the flight tunnel showed that only addition of the corresponding aldehyde to the major pheromone component Z9,E12-14:OAc raised the male response. A subtractive assay, however, revealed that the exclusion of any of the compounds from the complete four-compound blend reduced its activity significantly. We thus conclude that the female-produced sex pheromone of P. interpunctella consists of at least four components, i.e., Z9,E12-14:OAc, Z9,E12-14:Ald, Z9,E12-14:OH and Z9-14:OAc. In a field trapping test performed in a storage facility, the four-component blend attracted significantly more males of P. interpunctella than traps baited with Z9,E12-14:OAc alone. In contrast, the highest number of Ephestia kuehniella males was found in the traps baited with this major component, suggesting that the secondary pheromone components contribute to the species specificity of the blend.
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    URL: http://dx.doi.org/10.1023/A:1003703724011
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    Role of visual cues and interaction with host odour during the host-finding behaviour of the cabbage moth (1999)
    Springer
    Entomologia experimentalis et applicata 91 (1999), S. 59-65 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Noctuidae ; Mamestra brassicae ; host-finding behaviour ; visual cues ; host-choice ; interaction ; odour ; volatiles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The approach and landing responses of female Mamestra brassicae (L.) (Lepidoptera: Noctuidae) to visual cues from artificial plant leaves of different shapes and presence/absence of cabbage plant odour were investigated in a laboratory wind tunnel. The leaves were painted with cadmium yellow colour and observed under dim red light. Females showed oriented flight towards plant odours but landed significantly more often when the odour was presented with an artificial leaf. In three-choice tests, the shape of the leaf targets (circle, square or triangle) did not influence the female response. However, the size of the target did influence the insect response: the females preferred landing on square targets with sides of 5 or 10 cm rather than on the largest target, with sides of 15 cm. The orientation of the target influenced the insects' response: females landed significantly more often on the target positioned vertically than horizontally.
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    URL: http://dx.doi.org/10.1023/A:1003605125191
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    Cytochrome P450 Enzymes and Drug Metabolism—Basic Concepts and Methods of Assessment (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 309-323 
    Details
    ISSN: 1573-6830
    Keywords: cytochrome P450 ; enzyme inhibition ; enzyme induction ; pharmacokinetics ; drug interaction ; in vitro assessment ; clinical assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. The cytochrome P450 enzyme family is one of the major drug metabolizing systems in man. 2. Factors such as age, gender, race, environment, and drug treatment may have considerable influence on the activity of these enzymes. 3. There are now well-established in vitro techniques for assessing the role of specific cytochrome P450 enzymes in the metabolism of drugs, as well as the inhibitory or inducing effects of drugs on enzyme activity. In vitro data have been utilized to predict clinical outcomes (i.e., pharmacokinetic interactions), with close correlations between in vitro and in vivo data. 4. This information can be of considerable practical assistance to clinicians, to help with rational prescribing or to prevent or minimize the potential for drug interactions.
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    URL: http://dx.doi.org/10.1023/A:1006993631057
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    Chirality and Drugs Used in Psychiatry: Nice to Know or Need to Know? (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 355-372 
    Details
    ISSN: 1573-6830
    Keywords: enantiomers ; racemic ; chiral ; stereoselective ; pharmacokinetics ; cytochrome P450 ; geometric isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Many drugs used to treat psychiatric disorders contain a chiral center or a center of unsaturation and are marketed as a mixture of the resultant enantiomers or geometric isomers, respectively. These enantiomers or geometric isomers may differ markedly with regard to their pharmacodynamic and/or pharmacokinetic properties. 2. Examples of the effects of chiral centers or geometric centers on such properties are given for drugs from the following classes: antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, viloxazine, bupropion, trazodone, mianserin, venlaflaxine); benzodiazepines, zoplicone, and antipsychotics. 3. As described in this review, there are several notable examples of psychiatric drugs currently available where the individual enantiomers or geometric isomers differ considerably with regard to factors such as effects on amine transport systems, interactions with receptors and metabolizing enzymes, and clearance rates from the body. Indeed, relatively recent developments in analytical and preparative resolution of racemic and geometric drug mixtures and increased interest in developing new drugs which interact with specific targets, which have been described in detail at the molecular level, have resulted in increased emphasis on stereochemistry in drug development.
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    URL: http://dx.doi.org/10.1023/A:1006997731966
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    Metabolism of Tricyclic Antidepressants (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 373-409 
    Details
    ISSN: 1573-6830
    Keywords: antidepressants ; tricyclic ; metabolism ; hydroxy metabolites ; pharmacokinetics ; pharmacogenetics ; drug–drug interactions ; toxicity ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Despite the considerable advances in the treatments available for mood disorders over the past generation, tricyclic antidepressants (TCAs) remain an important option for the pharmacotherapy of depression. 2. The pharmacokinetics of TCAs are characterized by substantial presystemic first-pass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1 day (up to 3 days for protriptyline). 3. Clearance of tricyclics is dependent primarily on hepatic cytochrome P450 (CYP) oxidative enzymes. Although the activities of some P450 isoenzymes are largely under genetic control, they may be influenced by external factors, such as the concomitant use of other medications or substances. Patient variables, such as ethnicity and age, also affect TCA metabolism. The impact of gender and related reproductive issues is coming under increased scrutiny. 4. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. 5. Renal clearance of the polar metabolites of TCAs is reduced by normal aging, accounting for much of the increased risk of toxicity in older patients. 6. Knowledge of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications.
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    URL: http://dx.doi.org/10.1023/A:1006949816036
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    Metabolism and Pharmacokinetics of Selective Serotonin Reuptake Inhibitors (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 443-466 
    Details
    ISSN: 1573-6830
    Keywords: selective serotonin reuptake inhibitors ; metabolism ; pharmacokinetics ; fluoxetine ; fluvoxamine ; paroxetine ; sertraline ; citalopram ; cytochrome P450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Five drugs with the predominant pharmacologic effect of inhibiting the neuronal reuptake of serotonin are available worldwide for clinical use. This class of psychoactive drugs, known as selective serotonin reuptake inhibitors (SSRIs), is comprised of fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram. 2. The SSRIs appear to share similar pharmacodynamic properties which translate to efficacy in the treatment of depression and anxiety syndromes. The drugs are differentiated by their pharmacokinetic properties with regard to stereochemistry, metabolism, inhibition of cytochrome enzymes, and participation in drug–drug interactions. Studies focusing on the relationship of plasma drug concentration to therapeutic and adverse effects have not confirmed the value of plasma concentration monitoring. 3. This review summarizes the metabolism and relevant pharmacokinetic properties of the SSRIs.
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    Modulation of Flight Activity in Lobesia botrana Den. & Schiff. (Lepidoptera: Tortricidae) Females Studied in a Wind Tunnel (1999)
    Springer
    Journal of insect behavior 12 (1999), S. 199-211 
    Details
    ISSN: 1572-8889
    Keywords: Lepidoptera ; Tortricidae ; Lobesia botrana ; flight activity ; wind tunnel ; atmospheric pressure ; flight experience ; mating ; age ; olfaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We studied modulations of flight activity in European grapevine moth females (EGVM) by individual observations in a wind tunnel. The effect of different factors was analyzed: variation in atmospheric pressure prior to the experiments, time of day, first experience of flight, age, mating, and odor of tansy, which attracts females. The circadian flight activity showed a peak the hour preceding the onset of scotophase and sustained activity occurred during the 6 h around this peak. Females with a flight experience in the tunnel took off more quickly than naive ones (3.9 ± 7.4 vs 20.3 ± 22.8 s). Three-day-old unmated females subjected to negative variations of atmospheric pressure (10 hPa) during the 4 h prior to the experiments increased their duration of flight (12.1 ± 8.7 vs 5.3 ± 3.4 s) compared to those not subjected to variation. One-day-old females were less active than older ones; flight was shorter than in 2-day-old females (2.7 ± 6.7 vs 5.1 ± 9.5 s) and fewer of them took off (28 vs 63%). Mating also affected the flight activity of 2-day-old females; mated females flew longer than virgins (12 ± 16.8 vs 5.1 ± 9.5 s) and took off more quickly (6.5 ± 14.4 vs 19.3 ± 20.1 s). Tansy odor in the tunnel did not significantly affect the flight behavior of virgin females, but it increased the proportion of mated females that initiated flight (87 vs 70%) and duration of flight (11.2 ± 24.4 vs 7.2 ± 13.7 s), and it reduced the latency to takeoff (2.1 ± 7.4 vs 8.1 ± 19.1 s). Flight duration in tansy odor was inversely correlated with the total number of eggs laid during the female's whole life. Our experimental settings did not allow observation of movements directed toward the odor source.
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    Torch-light Transect Surveys for Moths (1999)
    Springer
    Journal of insect conservation 3 (1999), S. 15-24 
    Details
    ISSN: 1572-9753
    Keywords: census ; conservation ; Lepidoptera ; population monitoring ; survey techniques
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Abstract The use of light traps in sampling moth populations is an established technique used by entomologists and ecologists. However, trap data partly reflect the variable attractiveness of UV light to different species of moth. There are also potential problems of the practicality and expense of running traps in certain locations. An alternative method of recording moth populations is developed, using a modification of the transect count technique used for butterflies (Pollard and Yates, 1993) and recently applied to moths (Spalding, 1997). During transects, moths were observed by torch-light in a 5 by 5 m box, before the recorder walked on for 10 paces, and recorded moths in the next 5 m box. The transect approach was tested in the field, alongside traditional light trap and sugar methods. Transects recorded moth species for relatively little effort, produced repeatable measures of relative density, and provided habitat-specific data. This approach is likely to provide a valuable addition to light trapping in biodiversity inventories, species surveys, and in monitoring the effects of habitat management for conservation.
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    URL: http://dx.doi.org/10.1023/A:1009674321237
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    Bias in Butterfly Distribution Maps: The Effects of Sampling Effort (1999)
    Springer
    Journal of insect conservation 3 (1999), S. 33-42 
    Details
    ISSN: 1572-9753
    Keywords: mapping ; database ; bias recording ; monitoring ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Abstract Data from the Greater Manchester Butterfly Atlas (UK) reveal a highly significant and substantial impact of visits on both species' richness and species' incidence in squares. This effect has been demonstrated for three different zones mapped at different scales. The significant impact of number of visits persists when data are amalgamated for coarser scales. The findings demonstrate that it is essential for distribution mapping projects to record data on recording effort as well as on the target organisms. Suggestions are made as to how distribution mapping may be improved, including a geographically and environmentally representative structure of permanently monitored squares and closer links between distribution mapping and the Butterfly Monitoring Scheme (BMS), which primarily monitors changes in butterfly populations. The benefit to conservation will be data that can be better used to analyse the reasons for changes in ranges and distributions, fundamental for determining priorities and policy decisions.
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    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
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    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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    Sex Pheromone Components of Casuarina Moth, Lymantria xylina (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 2535-2545 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Lymantriidae ; Lymantria xylina ; Lymantria dispar ; Lymantria monacha ; Lymantria fumida ; sex pheromone ; reproductive isolation ; (7R,8S)-cis-7,8-epoxy-2-methyleicosane ; (7S,8R)-cis-7,8-epoxy-2-methyleicosane ; 2-methyl-Z7-eicosene ; (7R,8S)-cis-7,8-epoxy-2-methylnonadecane ; (7S,8R)-cis-7,8-epoxy-2-methylnonadecane ; (7R,8S)-cis-7,8-epoxy-3-methylnonadecane ; (7S,8R)-cis-7,8-epoxy-3-methylnonadecane ; disparlure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract cis-7,8-Epoxy-2-methyleicosane is a sex pheromone component of the Casuarina moth, Lymantria xylina Swinhoe. The compound was extracted from pheromone glands of female moths and was identified by coupled gas chromatographic–electroantennographic detection (GC-EAD) and GC–mass spectrometry. In field experiments in Taiwan, traps baited with either or both of (7R,8S)-cis-7,8-epoxy-2-methyleicosane (〉99% ee) [termed here (+)-xylinalure] and (7S,8R)-cis-7,8-epoxy-2-methyleicosane (〉99% ee) [termed here (−)-xylinalure] captured male L. xylina. Addition of further candidate pheromone components to xylinalure did not enhance its attractiveness. Demonstration of whether or not female L. xylina produce both optical isomers of xylinalure, and determination of the ratio, will require pheromone extract analyses on a chiral, enantiomer-separating column (as yet unavailable) or derivatization of epoxides in accumulated gland extracts. Attraction of male L. xylina to either enantiomer of xylinalure contrasts with enantiospecific production of, and/or response to, epoxy pheromones in congeners. With no other nocturnal lymantriid moth known in Taiwan to utilize xylinalure for pheromonal communication, enantiospecific “fine tuning” of xylinalure, or evolution of a more complex pheromone blend, may not have been necessary for L. xylina to maintain specificity of sexual communication. Racemic xylinalure will be appropriate for pheromone-based detection surveys of L. xylina in North America.
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    Identification and Field Evaluation of Components of Female Sex Pheromone of Millet Stem Borer, Coniesta ignefusalis (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 2643-2663 
    Details
    ISSN: 1573-1561
    Keywords: Coniesta ignefusalis ; Acigona ignefusalis ; Lepidoptera ; Pyralidae ; sex pheromone ; (Z)-7-dodecen-1-ol ; (Z)-5-decen-1-ol ; (Z)-7-dodecenal ; (Z)-7-dodecenyl acetate ; (Z)-9-tetradecen-1-ol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Five active compounds were detected during analyses of ovipositor washings and effluvia from virgin female Coniesta ignefusalis moths by gas chromatography (GC) linked to electroantennographic (EAG) recording from a male moth. These were identified as (Z)-7-dodecen-1-ol (Z7–12:OH), (Z)-5-decen-1-ol (Z5–10:OH), (Z)-7-dodecenal (Z7–12:Ald), (Z)-7-dodecenyl acetate (Z7–12:Ac), and (Z)-9-tetradecen-1-ol (Z9–14:OH) by comparison of their GC retention times, mass spectra, and EAG activities with those of synthetic standards. Laboratory tests of dispensers for these compounds showed that release rates from polyethylene vials increased to relatively uniform values after three to four days, but release from septa was very rapid and nonuniform and decreased to low levels after two to three days. Trapping tests in Niger showed that the major component, Z7–12:OH, and two of the minor components, Z5–10:OH and Z7–12:Ald, were essential for attraction of male C. ignefusalis moths. The most attractive blend contained these three components in a 100:5:3.3 ratio in a polyethylene vial, which emitted the components in similar proportions to those produced by the female C. ignefusalis moth. Water traps baited with this blend containing 1 mg of Z7–12:OH caught more male C. ignefusalis moths than traps baited with newly emerged female moths. Addition of up to 10% of the corresponding E isomers of the pheromone components had no effect on catches, but addition of the other two minor components detected, Z7–12:Ac and/or Z9–14:OH, to the attractive blend at naturally occurring levels caused significant reductions in trap catch.
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    Synergistic Sex Pheromone Components of White-Spotted Tussock Moth, Orgyia thyellina (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 1091-1104 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Lymantriidae ; white-spotted tussock moth ; Orgyia thyellina ; (Z)-6-heneicosen-11-one ; (Z)-6-heneicosen-9-one ; (Z)-6,(E)-8-heneicosadien-11-one ; sex pheromone ; synergism ; quarantine insect ; international trade ; eradication ; Bacillus thuringiensis ; microbial insecticide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract In 1996, the exotic white-spotted tussock moth (WSTM), Orgyia thyellina (Lepidoptera: Lymantriidae), was discovered in Auckland, New Zealand. Because establishment of WSTM would threaten New Zealand's orchard industry and international trade, eradication of WSTM with microbial insecticide was initiated. To monitor and complement eradication of WSTM by capture of male moths in pheromone-baited traps, pheromone components of female WSTM needed to be identified. Coupled gas chromatographic–electroantennographic detection analysis of pheromone gland extract revealed several compounds that elicited responses from male moth antennae. Mass spectra of the two most EAD-active compounds suggested, and comparative GC-MS of authentic standards confirmed, that they were (Z)-6-heneicosen-11-one (Z6–11-one) and (Z)-6-heneicosen-9-one, the latter termed here “thyellinone.” In field experiments in Japan, Z6–11-one plus thyellinone at a 100:5 ratio attracted WSTM males, whereas either ketone alone failed to attract a single male moth. Addition of further candidate pheromone components did not enhance attractiveness of the binary blend. Through the 1997–1998 summer, 45,000 commercial trap lures baited with 2000 μg of Z6–11-one and 100 μg of thyellinone were deployed in Auckland towards eradication of the residual WSTM population.
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    Behavioral Response of Female Codling Moths, Cydia pomonella, to Apple Volatiles (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 1343-1351 
    Details
    ISSN: 1573-1561
    Keywords: Host-plant volatiles ; apple ; Malus domestica ; reproductive behavior ; codling moth ; Cydia pomonella ; Tortricidae ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Apple volatiles stimulated pheromone release, oviposition, and upwind orientation in female codling moths, Cydia pomonella. Green apples increased the percentage of virgin females calling, the duration of female calling, and advanced the onset of egg-laying in gravid females. In a tube olfactometer, both virgin and mated females were more active in the presence of apple volatiles than in clean air. They responded by walking while wing-fanning; mated females showed a stronger attraction response than unmated females.
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    Pheromone Components and Diel Periodicity of Pheromonal Communication in Lymantria fumida (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 2305-2312 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Lymantriidae ; Lymantria fumida ; Lymantria monacha ; nun moth ; sex pheromone ; periodicity ; calling behavior ; reproductive isolation ; disparlure ; (7R,8S)-cis-7,8-epoxy-2-methyloctadecane ; (7S,8R)-cis-7,8-epoxy-2-methyloctadecane ; 2-methyl-Z7-octadecene ; (7R,8S)-cis-7,8-epoxy-octadecane ; (+)-monachalure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Extracts of pheromone glands from female Lymantria fumida were analyzed by coupled gas chromatographic–electroantennographic detection (GC-EAD) and by coupled GC–mass spectrometry (MS). The two compounds that elicited responses from male L. fumida antennae were identified as cis-7,8-epoxy-2-methyloctadecane (disparlure) and 2-methyl-Z7-octadecene (2me-Z7–18Hy). Field experiments in northern Japan demonstrated that synthetic (7R,8S)-cis-7,8-epoxy-2-methyloctadecane [(+)-disparlure] and 2me-Z7–18Hy are synergistic sex pheromone components of L. fumida. (7S,8R)-cis-7,8-Epoxy-2-methyloctadecane [(−)-disparlure] had no behavioral effect on male L. fumida. Traps baited with (+)-disparlure and 2me-Z7–18Hy captured male L. fumida between 21:00 and 24:00 hr, whereas traps baited with (+)-monachalure [(7R,8S)-cis-7,8-epoxy-octadecane], (+)-disparlure and 2me-Z7–18Hy attracted males of the nun moth, L. monacha L., between 02:00 and 04:00 hr. Both temporal separation of pheromonal communication and specificity of pheromone blends seem to contribute to the reproductive isolation of sympatric and coseasonal L. fumida and L. monacha.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020873807864
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  • 93
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    An Oviposition Stimulant for Spicebush Swallowtail Butterfly, Papilio troilus, from Leaves of Sassafras albidum (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 1233-1245 
    Details
    ISSN: 1573-1561
    Keywords: Swallowtail butterfly ; Papilionidae ; Papilio troilus ; Lepidoptera ; Lauraceae ; Sassafras albidum ; oviposition stimulant ; 3-trans-caffeoyl-muco-quinic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Female butterflies of the spicebush swallowtail, Papilio troilus, are specialists, ovipositing on plants in the family Lauraceae. Column chromatography and HPLC were used to isolate an oviposition stimulant from the leaves of one of its hosts, Sassafras albidum. The stimulant was identified as 3-trans-caffeoyl-muco-quinic acid on the basis of FAB-MS and 1H NMR spectra as compared to a compound previously isolated from another plant. It was not active alone, but it increased the oviposition activity of butterflies when combined with other stimulant(s) at a concentration of 7 ng/mm2 leaf surface area. Other caffeoylquinic acid isomers tested did not have this effect. This is the first report of a swallowtail contact oviposition stimulant from a plant in the family Lauraceae.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020962422712
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  • 94
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    Evolution and Adaptive Significance of Larval Midgut Alkalinization in the Insect Superorder Mecopterida (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 1945-1960 
    Details
    ISSN: 1573-1561
    Keywords: Insect–plant interaction ; midgut alkalinization ; phylogenetic distribution ; Mecopterida ; Diptera ; Lepidoptera ; Trichoptera ; polyphenolics ; alkylating agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The phylogenetic distribution of reported midgut pH values among larval Mecopterida supports a model in which the common ancestor of this group possessed an alkaline midgut, with subsequent loss of this trait in the lineage leading to the muscomorphan Diptera. The relationship between midgut pH and diet guild rank within the Lepidoptera and Diptera was tested by assigning numerical values to diet guilds (i.e., fruit, grasses, herbs, trees and shrubs, and organic detritus). Lepidopteran superfamilies were found to differ significantly in both midgut pH and in diet guild rank. Regression of mean superfamily midgut pH against mean superfamily diet guild rank yielded an R 2 of 0.79 (N = 10), whereas regression of species midgut pH against species diet guild rank yielded an R 2 of only 0.15 (N = 60). Species feeding on foliage of plant taxa high in tannins and on Solanaceae have midgut pH values above 9, and midgut pH in species feeding on these taxa is positively related to diet guild. In contrast, species feeding on the foliage of plant taxa containing terpenes, DIMBOA, glucosinolates, and pyrrolizidine alkaloids have midgut pH values near 8, and midgut pH of these species is either not related to diet guild (all species) or is negatively related to diet guild rank when the analysis is limited to the Noctuoidea. The data suggest that decreased midgut pH in species feeding on plants containing terpenes, DIMBOA, glucosinolates, and pyrrolizidine alkaloids may be an adaptive response that overrides selection for high pH in the presence of tannins and that midgut pH may be one factor contributing to the limitation of the host plant range of many species of lepidopteran herbivores.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020946203089
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  • 95
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    Volatile Stimuli Related to Feeding Activity of Nonprey Caterpillars, Spodoptera exigua, Affect Olfactory Response of the Predatory Mite Phytoseiulus persimilis (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 1585-1595 
    Details
    ISSN: 1573-1561
    Keywords: Tritrophic interactions ; Lima bean ; Phytoseiulus persimilis ; Tetranychus urticae ; Spodoptera exigua ; Acari ; Lepidoptera ; infochemicals ; herbivore-induced plant volatiles ; nonprey herbivores ; feces
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The effect of volatiles related to feeding activity of nonprey caterpillars, Spodoptera exigua, on the olfactory response of the predatory mites Phytoseiulus persimilis was examined in a Y-tube olfactometer. At a low caterpillar density (20 caterpillars on 10 Lima bean leaves), the predators were significantly more attracted to volatiles from infested leaves on which the caterpillars and their products were present or from infested leaves from which the caterpillars and their products had been removed when compared to volatiles from uninfested leaves. The predators, however, significantly avoided odors from 20 caterpillars and their products (mainly feces) removed from bean leaves. In contrast, at a higher caterpillar density (100 caterpillars on 10 Lima bean leaves), the predators avoided volatiles from caterpillar-infested bean leaves. Volatiles from infested leaves from which the caterpillars and their products had been removed were not preferred over volatiles from uninfested leaves. Volatiles from feces collected from 100 caterpillars were strongly avoided by the predators, while the behavior of the predatory mites was not affected by volatiles from 100 caterpillars removed from a plant. The data show that carnivorous arthropods may avoid nonprofitable herbivores. This avoidance seems to result from an interference of volatiles from herbivore products with the attraction to herbivore-induced plant volatiles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020888816525
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  • 96
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    A Novel Bioassay for Yponomeuta cagnagellus Oviposition in Response to Extracts of Host and Nonhost Plant Surface Compounds (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 2547-2559 
    Details
    ISSN: 1573-1561
    Keywords: Yponomeuta cagnagellus ; ermine moth ; Lepidoptera ; speciation ; specialization ; plant surface compounds ; oviposition ; host discrimination ; Euonymus europaeus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Yponomeuta cagnagellus is a phytophagous moth species specialized on Euonymus europaeus. Host discrimination by the adult female is an important aspect of host specialization and is based mainly on the distinctive secondary chemistry of host and nonhosts. This paper describes a bioassay that was developed to study the effect of isolated plant surface compounds on Yponomeuta oviposition. Adult moths recognize their hosts through chemical stimuli on the leaf or twig surface. Relatively apolar compounds extracted from the host twig surface by washing in dichlormethane do not stimulate oviposition. More polar, methanol-soluble compounds do, and this stimulation is dose dependent. Moths are able to recognize hosts solely by their surface compounds: females show a strong preference for artificial twigs treated with methanolic extracts of their hosts compared to those treated with methanolic extracts of nonhosts Crataegus monogyna and Prunus spinosa (both of which are hosts for closely related Y. padellus). Shape and surface characteristics of the oviposition substrate also influence oviposition. The substrate needs to resemble the basic form of a twig (i.e., cylindrical), and females prefer a coarse surface with irregularities over a smooth one.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020882326462
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  • 97
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    Characterization of Pheromone Blend for Grapevine Moth, Lobesia botrana by Using Flight Track Recording (1999)
    Springer
    Journal of chemical ecology 25 (1999), S. 389-400 
    Details
    ISSN: 1573-1561
    Keywords: Lepidoptera ; Tortricidae ; Lobesia botrana ; grapevine moth ; wind tunnel ; behavior ; flight track recording ; (E)-7,(Z)-9-dodecadienyl acetate ; (E)-7,(Z)-9-dodecadien-1-ol ; (Z)-9-dodecenyl acetate ; (E)-9-docecenyl acetate ; 11-dodecenyl acetate ; pheromone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The behavioral responses of Lobesia botrana males to calling females, pheromone gland extracts, and synthetic sex pheromones were recorded in a wind tunnel. Gland extracts and synthetic pheromones were released from a pheromone evaporator. The numbers of males reaching the source and their flight tracks in response to calling females and pheromone gland extracts were compared to those of synthetic blends. Upwind flights to natural sex pheromone were straighter and faster than to a three-component blend of (E)-7,(Z)-9-dodecadienyl acetate (E7,Z9–12:Ac), (E)-7,(Z)-9-dodecadien-1-ol (E7,Z9–12:OH), and (Z)-9-docecenyl acetate (Z9–12:Ac) (100:20:5). The optimum ratio of E7,Z9–12:OH and Z9–12:Ac to E7,Z9–12:Ac was found to be 5% and 1%, respectively. An additional seven compounds identified in the sex pheromone gland were investigated for their biological activity. Two unsaturated acetates, i.e., (E)-9-dodecenyl acetate (E9–12:Ac) and Δ11-dodecenyl acetate (Δ11–12:Ac), increased the number of males reaching the source as well as straightness, linear velocity, and decreased the track angle of upwind flight. Optimum response was obtained by releasing 10 pg/min E7,Z9–12:Ac in a mixture with 0.5 pg/min E7,Z9–12:OH, 0.1 pg/min Z9–12:Ac, 0.1 pg/min E9– 12:Ac and 1 pg/min Δ11-12–Ac. The saturated acetates previously identified in the female glands were biologically inactive.
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    URL: http://dx.doi.org/10.1023/A:1020811200054
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  • 98
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    Suitability of new and old association hosts for the development of selected microgastrine parasitoids of gramineous stemborers (1999)
    Springer
    Entomologia experimentalis et applicata 90 (1999), S. 257-266 
    Details
    ISSN: 1570-7458
    Keywords: host suitability ; acceptance ; biological control ; new associations ; Lepidoptera ; Pyralidae ; New World ; Old World ; stemborers ; Braconidae ; larval parasitoids ; Gramineae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The present study examined the acceptability and suitability of Old World stemborers (Chilo partellus and C. orichalcociliellus) for the development of New World parasitoids (Apanteles deplanatus and A. minator) and New World stemborers (Diatraea saccharalis and D. grandiosella) for the development of Old World parasitoids (Cotesia sesamiae, C. flavipes and C. chilonis). Results revealed that acceptance and suitability were high in old associations. In new associations, parasitoids accepted about 60% of the new association hosts. In addition, 10 out of 17 new associations were successful. Apanteles species appeared to be more physiologically host specific than Cotesia species. For example, two of four new association hosts were accepted by A. deplanatus and only one (D. saccharalis) was partially suitable for progeny development. Among the Cotesia species, Cotesia flavipes appeared to have a wider host range than the two other species. It attacked all hosts offered and successfully parasitized all but one (D. grandiosella). Diatraea saccharalis was accepted and was a suitable host for the development of all parasitoid species tested, whereas D. grandiosella was unsuitable for the development of four out of five parasitoid species tested. No clear pattern was observed as behavioral acceptance did not always agree with the pattern of physiological suitability. Implications of these findings for importation biological control of stemborers are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026435617979
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  • 99
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    Vive la variance: a functional oviposition theory for insect herbivores (1999)
    Springer
    Entomologia experimentalis et applicata 91 (1999), S. 187-194 
    Details
    ISSN: 1570-7458
    Keywords: oviposition ; strategy ; catastrophe ; theory ; clutch ; Lepidoptera ; optimization ; dynamic ; bet hedging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We developed state-dependent life-history theory to explain the variance in clutch size decisions made by insect herbivores under a variety of ecological scenarios. An important aspect of our theory is explicit representation of the distribution of host quality and frequency of occurrence. Examination of the theory suggests that clutch size decisions can be highly non-linear with respect to host quality and variability. We then use our theory to explore the potential for bet-hedging strategies to evolve as a function of unpredictable catastrophic events that decimate entire clutches. Our analysis suggests that the benefits to employing such a strategy will frequently be outweighed by costs brought on by delayed oviposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003622703384
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  • 100
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    The effects of mating, age at mating, and plant stimuli, on the lifetime fecundity and fertility of the generalist herbivore Epiphyas postvittana (1999)
    Springer
    Entomologia experimentalis et applicata 91 (1999), S. 287-295 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Tortricidae ; oviposition ; host deprivation ; lightbrown apple moth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects of mating, age at mating, the presence or absence of a plant leaf, and the deprivation of a suitable ovipositional substrate during when the first ovipositional bout after mating would normally take place, on the lifetime fecundity and fertility (percentage of fertile eggs laid) of female Epiphyas postvittana were investigated. Mating had a significant effect on lifetime fecundity, with mated females laying 2.5 times more eggs than virgin females. Age at mating had a significant effect on both fecundity and fertility, both declining with increasing age when the female was mated. In the presence of a leaf of C. japonica, mated females had a greater lifetime fecundity than when no leaf was present; females in the presence of a C. japonica leaf consistently laid more eggs each day during the first 4–6 days after mating than females without a leaf. When females were deprived of a suitable ovipositional substrate, for the first 22 h after mating, they were significantly less fecund over their lifetime than were control females. Finally, in no-choice tests with three plants of different acceptability to females, the fecundity of females differed in the order C. japonica 〉 Urtica ferox 〉 Tibouchina multiflora. This different fecundity appeared to be inversely related to the pubescence of the leaves, suggesting that leaf texture may be a suitable antixenotic resistance factor for crops to be protected from this insect. These results suggest that strategies whereby mating is delayed or oviposition reduced within a critical period after mating, may result in significant reductions in pest populations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003674529752
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