Perturbation in the 240Pu/239Pu global fallout ratio in local sediments following the nuclear accidents at Thule (Greenland) and Palomares (Spain)

Diabetes complicates 2-3% of all pregnancies and is associated with an increase in both perinatal morbidity and mortality, though reasons for these adverse outcomes are unknown. Estrogen biosynthesis is a critical factor during pregnancy and is carried out in the placenta via aromatase (cytochrome P450 19A1), which catalyzes the conversion of C-19 androgens to C-18 estrogens. Previous studies have shown that hormones such as insulin-like growth factors and insulin regulate aromatase activity when studied in vitro. Interestingly, levels of these hormones are altered in patients with diabetes. Thus, we hypothesized that the presence of maternal diabetes may alter placental aromatase activity and thus estrogen biosynthesis, possibly serving as one factor in the adverse outcomes of babies born to mothers with diabetes. To this end, we measured the production of 19-hydroxyandrostenedione, 19-oxoadrostenedione and estrone in 30 placental tissues from diabetic patients, using [7-3H]androst-4-ene-3,17-dione as a model substrate for aromatase (P450 19A1). A statistical difference was detected in the percentage of 19-oxoandrostenedione formed between the overt and control groups (P < 0.05). Additionally, NADPH P450-reductase levels were measured in these same tissues to determine whether alterations in this enzyme necessary for aromatase activity could be affected by diabetes. No differences in reductase levels were detected among the patient groups. However, a statistical correlation was found between NADPH P450-reductase activity and the formation velocities of all three estrogen products (P < 0.05). Thus, it appears that the presence of diabetes does not affect placental aromatase activity.     

Central motor conduction evaluation in glycogenosis type III

We report a 20-year-old man affected by glycogenosis type III with distal muscle weakness, more severe in distal leg muscles. The electromyogram showed myopathic features. Nerve conduction studies and central motor conduction after magnetic stimulation of the brain were normal. Our results suggest that there is no involvement of central motor pathways in this disease.     

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.     

Determination of dissociation constants of loop diuretics in acetonitrile-water mixtures

The dissociation pK values of the representative loop diuretics furosemide, bumetanide and ethacrynic acid in 10, 30, 40, 50 and 70% (w/w) acetonitrile-water mixtures at 298.15 K were determined, according to the rules and procedures endorsed by IUPAC. The variation in pK values over the whole composition range studied can be explained by tacking into account the preferential solvation of ionizable substances in acetonitrile-water mixtures. With a view to determining the pK values of the loop diuretics studied in any of the binary solvent acetonitrile-water mixtures, correlations of pK values and different bulk properties of the solvent were examined, and the linear solvation energy relationships method, LSER, has been applied. The pK values were then correlated with the pi*, alpha and beta solvatochromic parameters of acetonitrile-water mixtures. The resulting equations allowed us to calculate pK values for the loop diuretics in any acetonitrile-water mixture up to 70% (w/w) acetonitrile.     

Bladder pseudotumor in childhood

The application of frozen and radiation sterilized allogenic bone grafts for reconstructions in orthopaedic operations is described. Analysis of results of treatment of 1125 patients was performed. It was found that use of preserved bone allows to reduce the extend and duration of surgery. Nearly total substitution of grafts may be seen in 3 to 8 months after surgery.     

Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis

The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis. The results indicate that the binding of the peptide substrate or peptide inhibitor is entropically driven; i.e., it is characterized by an unfavorable enthalpy and a favorable entropy change, in agreement with a structure-based thermodynamic analysis based upon an empirical parameterization of the energetics. Dissection of the binding enthalpy indicates that the intrinsic interactions are favorable and that the unfavorable enthalpy originates from the energy cost of rearranging the flap region in the protease molecule. In addition, the binding is coupled to a negative heat capacity change. The dominant binding force is the increase in solvent entropy that accompanies the burial of a significant hydrophobic surface. Comparison of the binding energetics obtained for the substrate with that obtained for synthetic nonpeptide inhibitors indicates that the major difference is in the magnitude of the conformational entropy change. In solution, the peptide substrate has a higher flexibility than the synthetic inhibitors and therefore suffers a higher conformational entropy loss upon binding. This higher entropy loss accounts for the lower binding affinity of the substrate. On the other hand, due to its higher flexibility, the peptide substrate is more amenable to adapt to backbone rearrangements or subtle conformational changes induced by mutations in the protease. The synthetic inhibitors are less flexible, and their capacity to adapt is more restricted. The expected result is a more pronounced effect of mutations on the binding affinity of the synthetic inhibitors. On the basis of the thermodynamic differences in the mode of binding of substrate and synthetic inhibitors, it appears that a key factor to understanding resistance is given by the relative balance of the different forces that contribute to the binding free energy and, in particular, the balance between conformational and solvation entropy.