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  • Etoposide  (4)
  • Apomorphine  (3)
  • Daucus carota L. ssp. sativus  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Effects of haemopoietic growth factors in combination with etoposide on sister chromatid exchange frequencies in peripheral blood mononuclear cells (1998)
    Springer
    Cancer chemotherapy and pharmacology 41 (1998), S. 343-346 
    Details
    ISSN: 1432-0843
    Keywords: Key words Sister chromatid exchange ; Etoposide ; Stem-cell factor ; Interleukin 3 ; Granulocyte/macrophage colony-stimulating factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prior to work on the influence of dosing and scheduling of the drug etoposide in bone marrow cells, the DNA-damaging effects of three haemopoietic growth factors, either alone or in combination with etoposide, were investigated. Sister chromatid exchange (SCE) frequencies in phytohaemagglutinin-stimulated mononuclear cells of six normal volunteers were used as an indicator of DNA damage. The effects of three growth factors on SCEs were investigated at concentrations ranging between 0 and 100 ng/ml and those of etoposide alone, at concentrations varying between 0 and 2 μM. The effect of combinations of growth factor (GF) and etoposide were assessed at a 40-ng/ml concentration of each cytokine and at 0.4 μM etoposide. Results showed not only a dose-dependent rise in SCE frequency in cells treated with etoposide but also a cytokine effect. Stem-cell factor did not cause a significant change in SCE numbers. However, cytokines with activity at the progenitor cell level induced small but significant increases in SCE numbers at concentrations of 50 and 100 ng/ml (P〈0.001). Results of combination studies indicated a significant 60% increase in SCE numbers in cells treated with GF and etoposide as compared with etoposide alone (P〈0.00001). This finding suggests a sensitivity of peripheral blood mononuclear cells to SCE induction by GFs given either as single agents or in combination with etoposide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050749
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  • 2
    Electronic Resource
    Electronic Resource
    The progressive ratio schedule as a model for studying the psychomotor stimulant activity of drugs in the rat (1983)
    Springer
    Psychopharmacology 80 (1983), S. 184-189 
    Details
    ISSN: 1432-2072
    Keywords: Progressive ratio schedule ; Psychomotor stimulants ; Amphetamine ; Apomorphine ; Diazepam ; Imipramine ; Catecholamines ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Wistar rats were trained to press a lever with food reinforcement according to a continuously reinforced schedule (CRF). Afterwards, rats were subjected to three experimental sessions (30 min each) during which responding was rewarded according to a progressive ratio schedule (following an initial 2-min CRF period, the number of presses necessary for the pellet delivery was doubled every second minute). Responding during the first half of each session, i.e., pressing for food, was maintained at a significant level, whereas it was almost suppressed during the second part of the session. As compared to controls (200±20 presses/30 min) animals given amfonelic acid (0.5, 1 mg/kg IP), methylphenidate (4, 8 mg/kg IP), caffeine (16 mg/kg IP), cocaine (4 mg/kg IP), oxolinic acid (32 mg/kg IP), nomifensine (4 mg/kg IP), DR 250 (2, 4 mg/kg IP) and d-amphetamine (0.25, 0.5, 1 mg/kg IP) showed an increased rate of responding ranging from 400 to 950 presses/30 min. In contrast, apomorphine, MK 486+l-dopa, trihexyphenidyl, imipramine, salbutamol and diazepam did not increase responding. These results suggested that this test is highly sensitive for psychomotor stimulants and perhaps for their ability to enhance the reinforcing value of the reward or stimuli associated with the reward. Such activity seemed related to a catecholaminergic substrate since the increase of responding induced by amphetamine was blocked by pimozide, d,l-propranolol and prazosin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427967
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacological attempts to improve the bioavailability of oral etoposide (1995)
    Springer
    Cancer chemotherapy and pharmacology 37 (1995), S. 125-133 
    Details
    ISSN: 1432-0843
    Keywords: Etoposide ; stability ; pharmacokinetics bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Etoposide demonstrates incomplete and variable bioavailability after oral dosing, which may be due to its concentration and pH-dependent stability in artificial gastric and intestinal fluids. The use of agents that may influence etoposide stability and, thereby, bioavailability, was investigated in a number of clinical studies. Drugs that influence the rate of gastric emptying, while modulating the time of drug absorption, did not significantly alter the etoposide area under the concentration-time curve (AUC) or bioavailability. Specifically, metoclopramide had little effect on the etoposide absorption profile and did not significantly alter the AUC (AUC with etoposide alone, 68.4±20.3 μg ml−1 h, versus 74.3±25.9 μg ml−1 h with metoclopramide), suggesting that in most patients the drug is already emptied rapidly from the stomach. In contrast, propantheline produced a dramatic effect on etoposide absorption, delaying the time of maximal concentrationt max from 1.1 to 3.5 h (P〈0.01), but again without a significant improvement in drug AUC or bioavailability across the 24-h study period (AUC with etoposide alone 78.3±19.1 μg ml−1 h, versus 88.1±23.6 μg ml−1 h with propantheline). The effect of these drugs on the absorption of oral paracetamol, a drug included in the study as a marker of gastric emptying, was exactly the same as that found for etoposide, with no change in AUC being observed after metoclopramide or propantheline administration but a significant delay int max being seen on co-administration with etoposide and propantheline. The co-administration of ethanol or bile salts (agents that significantly improved the stability of etoposide in artificial intestinal fluid) with oral etoposide similarly had no effect on improving the etoposide AUC or reducing the variability in AUC, suggesting that drug stability in vivo was not affected by these agents. In the third study the co-administration of cimetidine had no effect on the pharmacokinetics of oral or i.v. etoposide, despite the previous observation that etoposide stability was markedly improved at pH 3–5 as compared with pH 1 in artificial gastric fluid. This series of studies, designed to investigate factors that improved etoposide stability in laboratory studies, failed to demonstrate any potentially useful improvement in AUC or bioavailability in the clinical setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685639
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  • 4
    Electronic Resource
    Electronic Resource
    Stability of the i.v. and oral formulations of etoposide in solution (1995)
    Springer
    Cancer chemotherapy and pharmacology 37 (1995), S. 117-124 
    Details
    ISSN: 1432-0843
    Keywords: Etoposide ; Stability ; Oral formulation Intravenous solution ; Stability-modulating agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Etoposide is a widely used cytotoxic drug that requires complex formulation for both the i.v. and oral preparation to ensure drug stability. Data on the stability of the i.v. formulation when diluted in infusion fluids are contradictory, and there is little information on the stability of the oral preparation in gastric or intestinal fluids. The stability of both i.v. and oral etoposide was therefore evaluated in the present investigation. The stability of the i.v. preparation was investigated across a range of concentrations in infusion fluids, being determined by regular sampling for highperformance liquid chromatography (HPLC) analysis and by visual inspection. The stability of the oral preparation was studied in both artificial gastric and intestinal fluids, again with regular sampling for HPLC analysis, and the influence of pH, concentration and the addition of ethanol and bile salts on oral stability was determined. The i.v. preparation showed a marked decrease in stability with increasing drug concentration, but stability was additionally reduced in i.v. bags regularly sampled with a syringe and needle as compared with bags that were inspected visually only (minimal stability in sampled bags, 24 h at 0.5 mg/ml and 5 h at 1.0 mg/ml, as compared with 10 days and 18 h at the respective concentrations in unsampled bags). Stability was also greater at room temperature, 20–23°C, as compared with 8–12°C. Loss of stability was indicated by a decrease in etoposide concentration (measured by HPLC) and the appearance of a fine white precipitate, shown to be pure etoposide. Importantly, the appearance of precipitate was as sensitive as a specific HPLC assay in detecting loss of stability and was in many cases apparent when the etoposide concentration was within 5% of the starting concentration. The oral formulation also showed a marked concentration-dependent decrease in stability in artificial intestinal fluid at pH 7.5 (percentage of etoposide in solution after 2 h at 0.5, 1.0, 1.5 and 2.0 mg/ml, 94±2%, 80±5%, 68±13% and 41±9%, respectively). There was no concentration effect on stability in gastric fluid at pH 3.0, although stability was much greater at pH 3 and pH 5 as compared with pH 1 or in intestinal fluid at pH 7.5. Stability in artificial intestinal fluid, pH 7.5, was also significantly improved by the addition of the bile salt sodium tauroglycocholate (2 mg/ml) at etoposide concentrations of 1 (P〈0.0001) and 2 mg/ml (P〈0.0001) and by the addition of ethanol (10%, v/v) at etoposide levels of 1 (P〈0.001) and 2 mg/ml (P〈0.001). These studies clearly demonstrate the concentration-dependent stability of both the i.v. and the oral formulation of etoposide, that the appearance of precipitate is a sensitive indicator of loss of stability in i.v. fluids, and that stability in artificial intestinal fluid can be modulated by the use of other agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685638
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  • 5
    Electronic Resource
    Electronic Resource
    Schedule-dependent topoisomerase II-inhibiting drugs (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. S84 
    Details
    ISSN: 1432-0843
    Keywords: Topoisomerase II ; Inhibition ; Etoposide ; Schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of topoisomerase II-acting drugs have been described, but few demonstrate schedule-dependent anti-tumour activity. The activity of the epipodophyllotoxins etoposide and teniposide and the acridine dye derivative amsacrine is clearly schedule-dependent, and this related not only to the observation that the activity of topoisomerase II varies throughout the cell cycle but also to the finding that these drugs are rapidly cleared from the cell following exposure, permitting DNA repair. Etoposide has been most clearly shown to be schedule dependent in clinical studies. The response rates of patients with small-cell lung cancer receiving a 24-h infusion was only 10% as compared with 89% when the same dose was given over 5 days. Pharmacokinetic studies performed in these patients demonstrated that although the total systemic exposure (area under the plasma concentration-time curve, AUC) was the same in both arms of the study, the duration of exposure to low levels of drug (〉1 μg/ml) was doubled in the 5-day arm. Haematological toxicity was the same in both arms of the study, as was the duration of exposure to higher plasma levels (〉5 μg/ml), suggesting that this toxicity may be associated with higher plasma concentrations, whereas anti-tumour activity is related to prolonged exposure to low levels of drug. This was confirmed in a subsequent study, where prolongation of treatment to 8 days compared to 5 days resulted in a similar exposure to low plasma concentrations and no difference in response rates or survival. Haematological toxicity in this study was worse in the 5-day arm, which also had an increased exposure to high levels of drug (〉5 μg/ml). More recently, interest has focused on even more prolonged etoposide administration, typically involving small daily doses repeated for 14–21 days. Although this schedule shows high activity in relapsed small-cell lung cancer and lymphoma, it is associated with significant toxicity (around one-third of patients experience grade III/IV leukopenia or neutropenia), which may be related to the observation that the etoposide dose delivered per course in these studies is higher than that obtained with standard dosing over 3–5 days. Further randomised studies are required to determine the optimal dose and schedule of etoposide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684869
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  • 6
    Electronic Resource
    Electronic Resource
    5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists (1992)
    Springer
    Psychopharmacology 108 (1992), S. 47-50 
    Details
    ISSN: 1432-2072
    Keywords: Yawning ; Penile erections ; (+) S-20499 ; 5-HT1A agonists ; D2 receptors ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4–5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10−8 M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 µg/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2–5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245284
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  • 7
    Electronic Resource
    Electronic Resource
    Inhibiteurs β-adrénergiques et stéréotypies provoquées par l'amphétamine ou l'apomorphine chez le rat (1972)
    Springer
    Psychopharmacology 23 (1972), S. 357-364 
    Details
    ISSN: 1432-2072
    Keywords: Propranolol ; Prinodolol ; Practolol ; Beta-Adrenergic Blocking Agents ; Amphetamine ; Apomorphine ; Stereotyped Behavior ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of three beta-adrenergic blocking agents was studied on the stereotyped behavior induced in rats by a range of doses of d-amphetamine or apomorphine. The stereotyped behavior was assessed either clinically (quotation from 0 to 3 at various times for each rat) or using the confinement motor activity test. From 8 mg/kg (i.p.) onwards, propranolol and prinodolol clearly potentiated the amphetamine-induced stereotyped behavior without any modification of the apomorphine-induced stereotyped behavior. Practolol, known for its poor passage through the blood-brain barrier had only a slight effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00406738
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  • 8
    Electronic Resource
    Electronic Resource
    Linkage relationships among molecular markers and storage root traits of carrot (Daucus carota L. ssp. sativus) (1999)
    Springer
    Theoretical and applied genetics 99 (1999), S. 58-64 
    Details
    ISSN: 1432-2242
    Keywords: Key words Genetic map ; RFLP ; AFLP ; RAPD ; SAMPL ; Daucus carota L. ssp. sativus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  A 109-point linkage map consisting of three phenotypic loci (P 1, Y 2, and Rs), six restriction fragment length polymorphisms (RFLPs), two random amplified polymorphic DNAs (RAPDs), 96 amplified fragment length polymorphisms (AFLPs), and two selective amplification of microsatellite polymorphic loci (SAMPL) was constructed for carrot (Daucus carota L. ssp. sativus; 2n=2x=18). The incidence of polymorphism was 36% for RFLP probes, 20% for RAPD primers, and 42% for AFLP primers. The overall incidence of disturbed segregation was 18%. Linkage relationships at a LOD score of 4.0 and θ=0.25 indicated 11 linkage groups. The total map length was 534.4 cM and the map was clearly unsaturated with markers spaced at 4.9 cM. AFLP P6B15 was 1.7 cM from P 1, AFLP P1B34 was 2.2 cM from Y 2, and AFLP P3B30XA was 8.1 cM from Rs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051208
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  • 9
    Electronic Resource
    Electronic Resource
    Evidence for maternal inheritance of the chloroplast genome in cultivated carrot (Daucus carota L. ssp. sativus) (1999)
    Springer
    Theoretical and applied genetics 98 (1999), S. 669-672 
    Details
    ISSN: 1432-2242
    Keywords: Key words Chloroplast DNA ; Daucus carota L. ssp. sativus ; Maternal inheritance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The incidence and inheritance of a chloroplast DNA (cpDNA) mutation/marker, BP10U, was studied in crosses among cultivated carrots (Daucus carota ssp. sativus). BP10U is about 400 bp larger than the more common BP10L allele. The occurrence of BP10U among carrot inbreds was widespread. Individual plants exhibited only one form of BP10, and cpDNA inheritance was strictly maternal. BP10U only occurred in male-fertile plants. Some male-fertile inbreds and all cytoplasmically male-sterile (petaloid) carrots had the BP10L allele. Alloplasmic cpDNA variation has been reported previously in Daucus, but this is the first report of variation and inheritance of cpDNA within cultivated carrot.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051119
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