RESUMEN
Localized variations at the nanoscale in soil aggregates and in the spatial organisation of soil organic matter (SOM) are critical to understanding the factors involved in soil composition and turnover. However soil nanoscience has been hampered by the lack of suitable methods to determine soil biophysical properties at nanometre spatial resolution with minimal sample preparation. Here we introduce for the first time an Atomic Force Microscopy (AFM)-based Quantitative Nano-Mechanical mapping (QNM) approach that allows the characterisation of the role of SOM in controlling surface nano-mechanical properties of soil aggregates. SOM coverage resulted in an increased roughness and surface variability of soil, as well as in decreased stiffness and adhesive properties. The latter also correlates with nano- to macro-wettability features as determined by contact angle measurements and Water Drop Penetration Time (WDPT) testing. AFM thus represents an ideal quantitative tool to complement existing techniques within the emerging field of soil nanoscience.
RESUMEN
The metabolism of a group of quinoline 3-carboxamide derivatives was evaluated in liver microsomes from various species. In addition, metabolism data were compared with in vivo pharmacokinetics in the mouse. The studied compounds were metabolized by cytochrome P450 enzymes. Microsomal clearance was low and seemed independent of a substituent in the quinoline moiety, whereas clearance was enhanced when an ethyl group replaced the methyl group at the carboxamide position. A similar metabolism with hydroxylated and dealkylated metabolites was found in the various species, with quantitative differences due to substituent. As predicted from the in vitro studies, in vivo pharmacokinetics showed low clearance and thus high exposure of the parent compounds in the mouse. The therapeutic effect seen in the acute EAE mouse model for these related compounds seems dependent on the high exposure of parent compound rather than formation of any potentially active metabolites.
Asunto(s)
Hidroxiquinolinas/farmacocinética , Microsomas Hepáticos/metabolismo , Animales , Células Cultivadas , Femenino , Humanos , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos C57BL , Conejos , Ratas , Especificidad de la EspecieRESUMEN
Three phenotypically different clonal human glioma cell lines were injected stereotactically into nude-rat brains, to determine their individual growth potential and to establish an in vivo system in which different therapeutic modalities could be tested. As assessed by serial sectioning, microscopic evaluation, and computer analysis, the mean approximate tumour volume after 3-7 weeks in vivo was 0.42 mm(3) for U-343 MG, 2.6 mm(3) for U-343 MGa Cl2:6, and 50.3 mm(3) for U-343 MGa 31L. When compared with the initial injected cell volume, only U-343 MGa 31L had increased in size, U-343 MGa Cl2:6 remained approximately the same but showed a certain proliferative potential, and U-343 MG regressed. Thus, only U-343 MGa 31L cells had high tumorigenic potential, invaded and replaced brain tissue in every direction, while U-343 MGa Cl2:6 cells grew in sheet-like tumour extensions along white-matter nerve-fibre tracts, in this respect mimicking foetal astrocytes. The tumorigenic potential of the U-343 MGa 31L cell clone was associated with a variable phenotype, as observed when the in vivo and in vitro characteristics were compared. The in vivo phenotype was characterized by the loss of GFAP immunoreactivity, the gain of heterogeneously distributed cellular tenascin, fibronectin, and laminin, but absence of extracellularly deposited material, and by the formation of irregular vessels. It appears that the intrinsic capacity of glioma cells to adapt to in vivo conditions is decisive for their tumorigenicity in the brain, rather than any single phenotypic property in itself. Moreover, the 2 glioma cell clones best suited for in vitro growth were no longer tumorigenic.
Asunto(s)
Neoplasias Encefálicas/patología , Glioma/patología , Trasplante de Neoplasias , Animales , Encéfalo , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/metabolismo , Células Clonales , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Glioma/irrigación sanguínea , Glioma/metabolismo , Humanos , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/metabolismo , Masculino , Fenotipo , Ratas , Ratas Desnudas , Células Tumorales CultivadasRESUMEN
The localization of the prostaglandin F2alpha (FP) receptor was examined in rat tissues by immunohistochemistry and in situ hybridization. Immunohistochemistry on paraffin sections was performed with a rabbit polyclonal antiserum raised against a synthetic peptide derived from the rat FP receptor sequence. In situ hybridization on cryosections was done with 35S-labelled rat FP receptor antisense and sense riboprobes. The most intense FP receptor-like immunoreactivity was observed in granulosa luteal cells, muscle and epithelial cells, e.g. cardiac, skeletal and smooth muscle, and hepatocytes. Weaker immunoreactivity was found in connective tissue fibroblasts. In the eye, intense immunostaining was associated with the corneal and conjunctival epithelium and moderate staining with the ciliary body, retina, iris and connective tissues. In situ hybridization generally confirmed the results. The riboprobe hybridized weakly with the heart, skeletal muscle, uterus, liver, lung and corpus luteum. Thus, the prostaglandin FP receptor was found to be widely distributed in rat tissues.