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  • 1
    Electronic Resource
    Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018945529611
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  • 2
    Electronic Resource
    Electronic Resource
    Distribution of Gacyclidine Enantiomers in Spinal Cord Extracellular Fluid (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 148-153 
    Details
    ISSN: 1573-904X
    Keywords: enantiomers ; extracellular fluid ; gacyclidine ; micro-dialysis ; spinal cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Determination of the pharmacokinetics of gacyclidineenantiomers, a non-competitive NMDA antagonist, in plasma and spinal cordextracellular fluid (ECF) of rats. Methods. Implantation of microdialysis probes in spinal cord (T9).Serial collection of plasma samples and ECF dialysates over 5 hoursafter IV bolus administration of (±)-gacyclidine (2.5 mg/kg). Plasmaprotein binding determined in vivo by equilibrium dialysis. ChiralGC/MS assay. Results. Plasma concentrations of (+)-gacyclidine were ∼25% higherthan those of (−)-gacyclidine over the duration of the experiment inall animals. Plasma concentrations decayed in parallel in a biphasicmanner (t1/2α ∼9 min; t1/2β ∼90 min) with no significant differencebetween enantiomers. Clearance and volume of distribution of(−)-gacyclidine were approximately 20% higher than those of its opticalantipode (CL: 248 vs 197 ml.kg−1.min−1;Vdβ: 31.6 vs 23.5 l/kg).Protein binding (∼90%) was not stereoselective. Both gacyclidineenantiomers were quantifiable in spinal cord ECF 10 min after drugadministration and remained stable over the duration of the experimentin spite of changing blood concentrations. Penetration of(−)-gacyclidine was significantly higher (∼40%) than that of (+)-gacyclidine inall animals. Yet, exposure of spinal cord ECF was similar for bothenantiomers, and not correlated with plasma AUCs. Conclusions. The disposition of gacyclidine enantiomers isstereoselective. Both enantiomers exhibit a high affinity for spinal cord tissueand their distribution may involve a stereoselective and active transportsystem. This hypothesis could also explain the discrepancy betweendrug concentrations in plasma and spinal cord ECF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007557028313
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  • 3
    Electronic Resource
    Electronic Resource
    Investigation of Nonimmune Hydrops Fetalis: Multidisciplinary Studies Are Necessary for Diagnosis—Review of 94 Cases (1999)
    Springer
    Pediatric and developmental pathology 2 (1999), S. 432-439 
    Details
    ISSN: 1615-5742
    Keywords: Key words: hydrops fetalis, abortions, chromosome abnormalities, infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT This review of 94 cases of nonimmune hydrops fetalis (NIHF) over a 10-year period was undertaken to evaluate the frequency of this pathology among fetal and infant deaths and to determine the most common likely etiologies in a northeastern region of France. NIHF represented 6% of the fetal deaths examined in our laboratory. The combination of findings from morphologic examination of the placenta and fetus with the results of microbiological and cytogenetic investigations (conventional cytogenetic study, fluorescent in situ hybridization [FISH], or DNA ploidy image analysis) led to an etiologic diagnosis for NIHF in two-thirds of the cases and suggested a diagnosis in an additional 23% of cases. The most common causes of NIHF were chromosome abnormalities (33%), infections (16%), and cardiac pathology (13.8%). The detection of a cause for NIHF is important for genetic counseling and management of subsequent pregnancies. Our experience suggests that a diagnosis is possible in a large majority of NIHF when obstetricians and pathologists carefully coordinate the management of prenatal and postnatal investigations and when new techniques, such as molecular biology and DNA quantification, are used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100249900146
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  • 4
    Electronic Resource
    Electronic Resource
    Synthesis and expression of laminin during human foetal lung development (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 242 (1995), S. 233-241 
    Details
    ISSN: 0003-276X
    Keywords: Laminin ; Lung ; Human Foetus ; Development ; Immunohistochemistry ; In situ hybridization ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Backgrounds: The lung develops by epithelial tubes budding and branching into a flexible mesenchyme. This growth is associated with the remodelling of the epithelial basement membrane, of which laminin is a major component. Methods: Both the synthesis and expression of laminin were studied in the human lung between 10 and 31 weeks of gestation, using in sity hybridization and immunohistochemistry. Results: The synthesis of the β chain was active in the epithelial and surrounding mesenchymal cells. The mRNAs coding for the γ chain were less abundant and mainly found in the epithelium. The synthesis of these two chains continued throughout gestation, and no significant difference in the density of hybridization grains could be detected between the tips of the expanding buds and the proximal portions. Immunohistochemical localization of laminin showed important modifications of the basement membrane during gestation. In the first part of the pseudoglandular stage the epithelial basement membrane stained continuously for laminin. Later, the basement membrane was labelled in a graded fashion: at the apex of the growing buds the staining became weak with focal disruptions. Both epithelial and mesenchymal synthesis of laminin remained active, while the polypeptide was undetectable using immunohistochemistry. Conclusions: These findings suggest that the remodelling of the basement membrane during human lung morphogenesis is probably not related to a decreasing synthesis of laminin, but to either a proteolytic degradation or the assembly of an inadequate complex undetectable with the polyclonal antibody antilaminin. © 1995 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1092420213
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