Rate of tetracycline dissolution from tablets and capsules and the biological availability of the antibiotic

Relation between the rate of tetracycline dissolution from tablets and capsules and the biological acceptibility of the antibiotic in the host was studied. The antibiotic dissolution rate from the pharmaceutical forms was determined in a modernized apparatus "Rotary basket" in water, the speed of the basket rotation was 200 r.p.m. In addition the tetracycline blood levels in patients treated with the drug in the above pharmaceutical forms were estimated. It was found that the rate of the antibiotic dissolution characterized the antibiotic biological acceptibility. A test for the dissolution rate was developed. It may be used for estimation of production batches of tetracycline tablets.     

Possibility of developing low-power reactors with a pebble-bed core

The possibilities of a two-section pebble-bed core with coolant delivered along the radial direction are examined for a water-cooled water-moderated 100–400 MW(t) reactor with 4 mm in diameter fuel pebbles. The construction of the two-section core includes two ring-shaped fuel layers (inner and outer) separated by a ring-shaped channel for coolant delivery. Water filters through the inner fuel layer from the periphery toward the center and through the outer layer from the center toward the periphery. The basic characteristics of such a reactor are determined. It is shown that the power density of such a core with 4 mm in diameter fuel pellets is two times higher than that in a VVÉR-1000 reactor, and there is a substantial margin with respect to the average specific heat flux. Thermohydraulic and neutron-physical calculations showed that two-section pebble-bed cores in low-power nuclear power reactors are promising.Translated from Atomnaya Énergiya, Vol. 97, No. 3, pp. 168–172, September, 2004.     

Engineering an enzyme to resist boiling

In recent years, many efforts have been made to isolate enzymes from extremophilic organisms in the hope to unravel the structural basis for hyperstability and to obtain hyperstable biocatalysts. Here we show how a moderately stable enzyme (a thermolysin-like protease from Bacillus stearothermophilus, TLP-ste) can be made hyperstable by a limited number of mutations. The mutational strategy included replacing residues in TLP-ste by residues found at equivalent positions in naturally occurring, more thermostable variants, as well as rationally designed mutations. Thus, an extremely stable 8-fold mutant enzyme was obtained that was able to function at 100 degrees C and in the presence of denaturing agents. This 8-fold mutant contained a relatively large number of mutations whose stabilizing effect is generally considered to result from a reduction of the entropy of the unfolded state ("rigidifying" mutations such as Gly --> Ala, Ala --> Pro, and the introduction of a disulfide bridge). Remarkably, whereas hyperstable enzymes isolated from natural sources often have reduced activity at low temperatures, the 8-fold mutant displayed wild-type-like activity at 37 degrees C.     

Human placental morphology as an index of features of maternal-fetal relationships

Principle possibilities of the complex evaluation of the mother-fetus exchange were studied by means of morphological investigations of the human placenta in normality, in vesicular mole, late toxicoses, hemolytic disease of newborns and malformations of the fetus. The investigation of the ratio of the villi of different size, deposition of fibrinoid on their surface, the change of the amount of cytotrophoblastic elements, cells of Kaschenko-Hofbauer and the polymerity of the basic substance are of diagnostic value. The authors propose the basal lamina of the placenta to be included into the scheme of the examination of placenta.     

Model building of a thermolysin-like protease by mutagenesis

The present study concerns the use of site-directed mutagenesis experiments to optimize a three-dimensional model of the neutral protease of Bacillus subtilis (NP-sub). An initial model of NP-sub was constructed using the crystal structures of the homologous neutral proteases of Bacillus thermoproteolyticus (thermolysin) and Bacillus cereus as templates. The largest portion of NP-sub could be modelled satisfactorily, using standard techniques, but several surface-located regions could only be modelled with a high degree of uncertainty. In order to make the model more reliable in these regions a 'model building by mutagenesis' approach was adopted. Mutations were designed such that their effect on thermal stability could indicate how their local environment should be modelled. This approach provided insight in the local structure of several regions in NP-sub that were hard to model on the basis of homology with the two known structures alone.