Comparative incidence of reticuloendothelial tumors in C57BL mice after exposure to tritiated water

A total of 2,377 C 57 Bl/6M mice were assigned to control groups and experimental groups exposed to tritiated water administered as a pulse injection or in drinking water, at a dose of 1.0 microCi per injection or per ml of drinking water. Weanlings were observed for the duration of life span. Data analysis was based on two coefficient estimates (1) individual carcinogenic induction coefficient and (2) specific tumorigenic induction coefficient. The carcinogenic potency of tritium was found to be dual in nature in enhancing the absolute induction of lymphocytic lymphomas in both sexes as well as their relative induction in competition with reticulo-endothelial tumors of other types.     

Desensitization of the δ-Opioid Receptor Correlates with Its Phosphorylation in SK-N-BE Cells: Involvement of a G Protein-Coupled Receptor Kinase

Abstract: Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human δ-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human δ-opioid receptor, revealed that it corresponded to the δ-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the δ-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the δ-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn²⁺, known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human δ-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK.     

Purification of human plasma fibronectin by double affinity chromatography on gelatin and heparin-Trisacryl

In this work the human plasma fibronectin was purified by affinity chromatography using a tandem column system. The first affinity column was filled with gelatin-Trisacryl whereas the second one contained heparin-Trisacryl. This double affinity chromatography demonstrated its high efficiency in term of purity and yield. Several analytical methods (electrophoresis, immunoelectrophoresis, F.P.L.C. and adhesion assay on cultured eucaryotic cells) evidenced in fact the high purity of the preparation as well as its biological behaviour in term of cell adhesion and spreading. The performances of the sorbents used facilitate the scaling up when large quantities of FNP are needed.     

Thrombopoietic activity induced by blood withdrawal and administration of antithrombocyte serum in nephrectomized rats. Role of kidneys in the production of thrombopoietin

The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.     

Determination of the inorganic degradation products sulfate and sulfamate in the antiepileptic drug topiramate by capillary electrophoresis

A capillary electrophoresis (CE) method has been developed as an alternative method for the determination of the inorganic degradation products sulfate and sulfamate in topiramate drug product and drug substance, currently performed by ion chromatography. The anions are separated in a background electrolyte containing potassium chromate and boric acid, followed by indirect UV detection. By adding tetradecyltrimethylammonium bromide to the electrolyte, analysis is performed under co-electroosmotic flow conditions. Variations in injection volumes and migration times are compensated for by use of an internal standard. The validation of the method, which was performed according to ICH guidelines (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) [1], comprises specificity, accuracy, linearity, precision, sensitivity and robustness. In addition, the results of an actual tablet sample analysis obtained by this CE method are statistically shown to be in close agreement with those obtained by an ion chromatographic method.