Correction of increased prostacyclin synthesis in Bartter's syndrome by indomethacin treatment

The role of prostacyclin and thromboxane A2 in the pathogenesis of Bartter's syndrome was investigated by measurement of the urinary excretion of 6-keto-PGF1 alpha and thromboxane B2, respectively, in five patients. The prostaglandin metabolites were extracted from urine by a reproducible method and measured by specific radioimmunoassays. The patients with Bartter's syndrome excreted about four-times as much 6-keto-PGF1 alpha as the normal controls. In contrast, there was no significant difference in the urinary excretion of thromboxane B2 between the patients and the controls. In a second part of the study, three patients were treated with indomethacin (150 mg/day for four days), an inhibitor of prostaglandin synthesis. This regimen suppressed urinary excretion of 6-keto-PGF1 alpha by 43% and that of thromboxane B2 by 46%. It is suggested that the increase in prostacyclin production is responsible for both the hyperreninemia and and the other endocrine derangements as well as the hyporesponsiveness of blood pressure to intravenous infusion of vasopressors in patients with Bartter's syndrome.     

The effect of the cyclin-dependent kinase inhibitor olomoucine on cell cycle kinetics

The effect of the cyclin-dependent (CDK) inhibitors olomoucine and roscovitine on cell kinetics was studied. To this end, nonsmall cell lung cancer (NSCLC) cell line MR65 and neuroblastoma cell line CHP-212 were pulse labeled with bromodeoxyuridine (BrdUrd) and chased in culture medium, to which various concentrations of olomoucine or roscovitine were added. A dose-dependent inhibition of the G1/S-phase and G2/ M-/G1 transitions was observed. Furthermore, S-phase progression was also inhibited in a dose-dependent manner. Similarly, roscovitine, another CDK inhibitor with a 10-fold higher efficiency for both CDK1 and CDK2 as compared to olomoucine, showed the same effects at a 10-fold lower concentration. At the highest tested doses both olomoucine (200 microM) and roscovitine (40 microM) induced a complete cell cycle block in both cell lines, paralleled by the appearance of apoptotic figures. In these cultures a decrease in CDK1 protein level was found as shown by Western blotting. Bivariate CDK1/DNA analysis confirmed these observations and showed that a subpopulation of cells with characteristics of apoptosis became CDK1 negative. The presented data suggest that cyclins and CDKs are involved at an important nodal point shared by pathways regulating cellular proliferation and apoptosis.     

Double sodium and potassium sulphates revealed by microprobe analysis in dried cervical mucus: a mid-cycle crystallographic index

The use of physical techniques such as scanning electron microscopy and microprobe analysis permits the analysis of valuable details of the structure of dried samples of mid-cycle cervical mucus during the period of maximum ferning. From a crystallographic point of view, particular attention was paid to the location, morphology and chemical composition of anisotropic organic sulphate microstructures. As distinct from the isotropic sodium chloride pattern described by Papanicolaou, these appear in a narrow period of time corresponding to the middle of the period of maximum ferning. Anisotropic microstructures were revealed to be tiny isolated crystals or polycrystalline aggregates composed of double salts of potassium and sodium. The potassium/sodium cation ratio, equal to 3/1, was constant in the best specimens. Using a simple polarizing microscope, the detection of anisotropic microstructures may be useful to determine the period of maximum fertility more accurately. In addition, experiments have been carried out in order to determine the relative importance of sulphate anisotropic structures as compared with the whole crystallized surface and to investigate precisely their transience after they appear.     

Towards a modelling of RPV steel brittle fracture using crystal plasticity computations on polycrystalline aggregates

In the frame of the multi-scale approach of the fracture toughness prediction defined in the PERFECT project, we proposed a new crystal plasticity model and applied it to the computation of stress heterogeneities within a reference polycrystalline aggregate defined in the project RPV material.The proposed crystal plasticity model is able to take into account the effects of temperature and irradiation hardening. The analysis of the results of aggregate computations shows that the distributions of the maximum values of the maximal principal stresses are found to be well described by a Gumbell function. Applying these distributions on a Griffith criterion allows settling the basis of an original fracture criterion. However the increasing resistance to fracture of the steel with temperature can be reproduced only by introducing a temperature dependence of the fracture energy.