Cost of the treatment of acute cerebrovascular insufficiency causing cerebral infarction]

Many countries are interested in the cost of therapy of the acute cerebral flow insufficiency leading to brain infarction. Total costs include: drugs, laboratory tests, nursing care, the cost of patients' food, equipment, amortization, hospital administration etc. The total expenditure for a 10-15-day treatment of the acute neurological incident depended on the severity of the disease and was 8 million ++ z?oty in case of mildly ill patient, 9 million in case of moderately severe disease, and 21 million z?oty in case of severely ill patient. If the costs of such tests as CT and TCD-scanning will be added, total cost will increase significantly.     

Interaction between the Msh2 and Msh6 Nucleotide-binding Sites in the Saccharomyces cerevisiae Msh2-Msh6 Complex

Indirect evidence has suggested that the Msh2-Msh6 mispair-binding complex undergoes conformational changes upon binding of ATP and mispairs, resulting in the formation of Msh2-Msh6 sliding clamps and licensing the formation of Msh2-Msh6-Mlh1-Pms1 ternary complexes. Here, we have studied eight mutant Msh2-Msh6 complexes with defective responses to nucleotide binding and/or mispair binding and used them to study the conformational changes required for sliding clamp formation and ternary complex assembly. ATP binding to the Msh6 nucleotide-binding site results in a conformational change that allows binding of ATP to the Msh2 nucleotide-binding site, although ATP binding to the two nucleotide-binding sites appears to be uncoupled in some mutant complexes. The formation of Msh2-Msh6-Mlh1-Pms1 ternary complexes requires ATP binding to only the Msh6 nucleotide-binding site, whereas the formation of Msh2-Msh6 sliding clamps requires ATP binding to both the Msh2 and Msh6 nucleotide-binding sites. In addition, the properties of the different mutant complexes suggest that distinct conformational states mediated by communication between the Msh2 and Msh6 nucleotide-binding sites are required for the formation of ternary complexes and sliding clamps.     

Excitation of a magnetospheric MHD cavity by Kelvin-Helmholtz instability

The Kelvin-Helmholtz instability is investigated analytically by using a one-dimensional nonuniform model of the Earth’s magnetosphere and the adjacent solar wind region. Its properties are shown to be essentially governed by the presence of an MHD cavity that arises in the magnetosphere because of the non-uniformity of the latter and also because of the jump in the parameters of the medium at the magnetopause (the outer boundary of the magnetosphere). System oscillations constitute a discrete spectrum of eigenmodes, which are determined by the wave vector k _t along the tangential discontinuity and also by the mode number n = 0, 1, 2, …, playing the role of the wavenumber along a coordinate normal to the magnetopause. Analytic expressions are obtained for the frequency and instability growth rate of each eigenmode and for the functions describing its spatial structure. All these quantities depend parametrically on the solar wind velocity V _W , or more precisely, on the Doppler frequency shift ω _W = k _t · V _W . For each eigenmode, there is a lower instability threshold depending on the parameter ω _W and a sharp maximum in the growth rate at the eigenfrequency of the magnetospheric cavity. For ω _W values below the threshold, the properties of an eigenmode are highly sensitive to the type of solar wind nonuniformity. Three cases are considered: a uniform solar wind and solar winds in which the speed of sound increases or decreases away from the magnetopause.     

Diffusion and diffusion-osmosis models of the transfer of charged molecules across biological barriers

Mathematical models of the transfer of large enough charged molecules (macroions) have been constructed on the basis of the classical equations of electromigration diffusion (Helmholtz-Smoluchowski, Goldman, and Goldman-Hodgkin-Katz). It is shown that ion transfer in placental barriers (mimicking lipid-protein membrane barriers) and in muscle barriers proceeds by different mechanisms. In placental barriers, the electromigration diffusion takes place through lipid-protein channels formed by conformational alteration of phospholipid and protein molecules, with diffusion coefficients D = (2.6–3.6) × 10⁻⁸ cm²/s. The transfer in muscle barriers is due to migration via charged interfibrillar channels with negative diffusion activation energy (explained by changes in the structure of muscle fibers and expenditures of thermal energy for the displacement of Cl⁻ from channel walls), and D = (6.0–10.0) × 10⁻⁶ cm²/s.     

Novel imidazole-based histamine H3 antagonists

A novel series of imidazole containing histamine H₃ receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22.