[Efficacy and safety of rivastigmine (exelon) in the confusion syndrome in the acute phase of ischemic stroke].

There is ample evidence that the poststroke confusion syndrome or delirium is a manifestation of cholinergic deficit. Given this conception, we conducted a controlled study of efficacy and safety of acetylcholinesterase inhibitor rivastigmine in patients developed a delirium in the acute phase of ischemic stroke. The study included 224 consecutive stroke patients: 68 patients developed a delirium in the acute phase of disease. Severity of delirium was scored with the Delirium Rating Scale (DRS). A main group included 21 patients with delirium treated with rivastigmine in individually tailored doses. A control group included 47 patients with delirium who received only vascular and anticoagulant treatment, i.e. haloperidol. Cognitive functions were tested 3 and 6 months after stroke with the MMSE, the FAB, the Luria 10 point verbal test. The Zarit Burden Interview (ZBI) was used after 3 and 6 months to measure caregiver burden. In patients treated with rivastigmine, the delirium phase was significantly shorter (p<0,001) compared to the control group. In patients without delirium in the acute phase of stroke, the results of neuropsychological study were better (p<0,001) than in patients with delirium. Total ZBI scores were more favorable in the rivastigmine group than in the control one (p<0,05). To the end of the study, 5 patients died in the rivastigmine group, 17 patients in the control group and 3 patients in the group without delirium. Rivastigmine was safe in the acute phase of stroke patients even after the rapid titration.

DNA-phospholipid recognition: modulation by metal ion and lipid nature. Complexes structure and stability calculated by molecular mechanics.

The structures and formation energies of nucleic acid-phospholipid complexes both in the absence and in the presence of Mg(2+) ions were calculated taking double-stranded trinucleoside diphosphates NpNpN or heptanucleotides ApAp(NpNpN)pApA, composed of 64 possible combinations of genetic code, and phosphatidylcholine (PC) and sphingomyelin (SM) as model compounds. The dependence of intramolecular interactions on the primary structure of nucleic acid molecules and on the presence of a cationic bridge was revealed. The formation energies and structure of oligonucleotides were found by molecular mechanics calculations with the AMBER force field. The structures of phospholipid and MgCl(2) molecules were calculated by the semiempirical PM3 method, while the energies of phospholipid-oligonucleotide complexes were calculated by the molecular mechanics method. Calculations of complexes were carried out with consideration of solvation effects. Considerable gain in the formation energy of triple complexes is achieved due to the presence of the electroneutral metal bridge. A tendency toward increasing the stability of "triple" PC complexes (but not SM ones), containing guanosine- and cytidine-enriched triplets was revealed. Depending on the structure of NpNpN trinucleotides, the formation energy values of NpNpN-MgCl(2)-PC and ApAp(NpNpN)pApA-MgCl(2)-PC complexes differ by 1.7-2.6 kcal mol(-1), which can be considered as the atomic-scale manifestation of the recognition phenomenon. Presence of metal (II) ion bridge results in a greater stabilization of the phospholipid-nucleic acid complexes for SM in comparison to PC (the total energy difference equals to 4-16 kcal mol(-1)). Depending on the structure of NpNpN trinucleotides, the formation energies of NpNpN-MgCl(2)-SM and ApAp(NpNpN)pApA-MgCl(2)-SM complexes differ by 1.7-2.1 kcal.mol(-1), which is essential at physiological conditions and can also be considered as the recognition effect.

Artificial protein vaccines with predetermined tertiary structure: application to anti-HIV-1 vaccine design.

A successful approach to the development of a safe and effective synthetic vaccine requires that different B and T cell epitopes of the infectious agent be included in the vaccine construction. In this paper we suggest a new approach to vaccine design in the form of an artificial protein with a predetermined tertiary structure (PTS vaccines). Based on B and T cell epitope properties, we substantiate the possible use for vaccine construction of one well-known protein spatial motif--the four-alpha-helix bundle. Antigenic determinants of cellular immunity (amphipathic alpha-helices) and humoral immunity (flexible hydrophilic loop regions) are used as blocks for vaccine design. General principles of PTS vaccine construction have been applied to anti-HIV-1 vaccine design.

[The effect of fixed water molecules on fractal properties of globular protein surfaces]. / Vliianie fiksirovannykh molekul body na fraktal'nye svoistva poverkhnostei globuliarnykh belkov.

On the base of the technique developed by the authors together with Schmidt the fractal properties of the 17 globular proteins have been analysed using the crystal structure data at high resolution. For all the proteins there are the coordinates of fixed water molecules in the protein data bank. For each protein the fractal dimension of its surface D has been calculated with and without taking into account the fixed water molecules located inside a 3-Angstrom hydrated layer. Small but systematic decrease of the DS values for the proteins with the fixed water molecules has been demonstrated. It means that the fixed water molecules tend to fill gaps on the protein surfaces and in that way to smooth the surfaces. The volumes and the molecular surfaces of the proteins have been also calculated on the base of the cube technique. The molecular surfaces of the proteins with the fixed water molecules prove to decrease. This fact can be considered as the indirect evidence that the protein surfaces become to be smoother.

Comparative study of thermostability and structure of close homologues--barnase and binase.

Parameters of heat denaturation and intrinsic fluorescence of barnase and its close homologue, binase in the pH region 2-6 have been determined. The barnase heat denaturation (pH 2.8-5.5) proceeds according to the "all-or-none" principle. Barnase denaturation temperature is lower than that of binase and this difference increases from 2.5 degrees C at pH 5 to 7 degrees C at pH 3. Enthalpy values of barnase and binase denaturation coincide only at pH 4.5-5.5, but as far as pH decreases the barnase denaturation enthalpy decreases significantly and in this respect it differs from binase. The fluorescence and CD techniques do not reveal any distinctions in the local environment of aromatic residues in the two proteins, and the obtained difference in the parameters of intrinsic fluorescence is due to fluorescence quenching of the barnase Trp94 by the His 18 residue, absent in binase. Secondary structures of both native and denaturated proteins also do not differ. Some differences in the barnase and binase electrostatic characteristics, revealed in the character of the dipole moments distribution, have been found.

[Comparison of the heat stability and structure close homologs--Bacillus amyloliquefaciens ribonuclease and Bacillus intermedius 7P ribonuclease]. / Sravneniee termostabil'nosti i struktury blizkikh gomologov-- ribonukleazy Bacillus amyloliquefaciens i ribonukleazy Bacillus intermedius 7P.

Parameters of heat denaturation and intrinsic fluorescence of barnase and its close homologue, binase, in the pH region 2-6 have been determined. Barnase heat denaturation (pH 2.8-5.5) proceeds according to the "all-or-none" principle. Barnase denaturation temperature is lower than that of binase and this difference increases from 2.5 degrees C at pH 5 to 7 degrees C at pH 3. Enthalpy values of barnase and binase denaturation coincide only at pH 4.5-5.5, but as the pH decreases the barnase denaturation enthalpy decreases significantly and in this respect it differs from binase. The fluorescence and CD techniques do not reveal any distinctions in the local environment of aromatic residues in the two proteins, and the obtained difference in the parameters of intrinsic fluorescence is due to fluorescence quenching of the barnase Trp-94 by the His-18 residue, which is absent in binase. Secondary structures of both native and denaturated proteins also do not differ. Some differences have been found in the barnase and binase electrostatic characteristics, revealed in the character of the dipole moment distribution.

[Comparative characteristics of changes in resected lungs in various forms of chronic nonspecific lung diseases studied by the radioisotope and pathomorphological methods]. / Sravnitel'naia kharakteristika izmenenii rezetsirovannykh legkikh pri nekotorykh formakh KhNZL po dannym radioizotopnogo i pato- morfologicheskogo issledovaniia.

The pathomorphological picture of 17 lungs resected for various forms of chronic nonspecific diseases of the lungs was compared with results of preoperative radioisotope studies. It was found that greater degree of decreased capillary blood flow in the lungs was followed by progressive growth of destructive, sclerotic alterations in the altered part of the lung, rearrangement of the vascular bed from the network type to the major vessel type took place. Similar comparison can help the clinic physician to disclose the real picture of the pathological process in the lungs.