[An effect of antipsychotic and anticholinergic treatment on cognitive function in patients with schizophrenia]. / Vliyanie antipsikhoticheskoi i antikholinergicheskoi terapii na kognitivnye funktsii u bol'nykh shizofreniei.

OBJECTIVE: To reveal the relationships between antipsychotic and anticholinergic drugs and cognitive functions in patients with schizophrenia. MATERIAL AND METHODS: The observational prospective study was conducted at the Bekhterev National Medical Center of Psychiatry and Neurology. The study involved 41 patients (22 men and 19 women) with paranoid schizophrenia, according to ICD 10 criteria, aged 30.12±8.24 years on stable antipsychotic monotherapy or in combination with anticholinergic drug (trihexiphenidyl). Cognitive functions were assessed using the «Brief Assessment of Cognitive Function in Patients with Schizophrenia¼ (BACS) scale, severity of mental state and extrapyramidal disturbances were measured using the «Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale for Assessment of Extrapyramidal Side Effects (SAS). All examination procedures were performed twice at weeks 2 and 8 of therapy. Patients were divided into 2 groups according to the type of antipsychotic therapy. Twelve patients received first generation antipsychotics (FGAs) (group 1), 29 patients received second generation antipsychotics (SGAs) (group 2). RESULTS: Patients receiving SGAs had a significant decrease in the overall SAS score at week 8 of therapy compared with data at week 2, and there was an improvement in cognitive function, unlike patients receiving FGAs. There were also changes on BACS tests the digit sequencing (V=51.5, p=0.007), token motor task (V=75.5, p=0.007) and Tower of London (V=52, p=0.027) only in patients of group 2. CONCLUSION: The improved tolerance to the drug, as well as cognitive measures, was shown in patients taking SGAs by week 8. Our study confirms the importance of adhering to the minimum effective dose of antipsychotic drugs for the treatment of schizophrenia to prevent cognitive impairment, and to give preference to SGAs in the choice of treatment.

[The choice of antibiotic in microbiological study of pyoinflammatory processes.]

The efficiency of application of test-system "Antibiotic Choice" was examined concerning evaluation of sensitivity to medications of maximal possible number of bacteria from pathological samples at burn trauma without isolation of pure culture. The results of metagenome analysis demonstrated that test-system permits supporting factually all bacteria discovered in wound discharge, including ones related to not cultivated yet. The comparison was carried out concerning results of standard identification of sensitivity of bacteria to antibiotics and efficient medication according the results of application of test-system "Antibiotic Choice". The obtained results demonstrate that test-system permits choosing antibiotic during 6-20 hours without separation of pure culture.

[CHOOSING ANTIBIOTIC IN MICROBIOLOGICAL ANALYSIS OF INFECTIONS OF URINARY EXCRETION SYSTEM].

The effectiveness of application of test-system "Choice of antibiotic" was evaluated as a tool for incubation of maximal amount of bacteria from pathological material under acute cystitis. The results of meta-genome analysis established that test-system permits supporting growth of practically all bacteria detected in urine, including ones relating to "uncultivated for the present". The comparison of results of standard detection of sensitivity of bacteria to antibiotics and identification of effective pharmaceutical according the results of application of test-system "Choice of antibiotic" as well was implemented It is demonstrated that test- system permits choosing antibiotic during 6-20 hours wiihout isolation of pure strain.

[Blood traces on the clothes of the alleged criminals and their significance for the inquiry into the killings].

The present analysis of blood traces on the clothes of the alleged criminals is based on the results of 109 medical criminalistic expertises. They are illustrated by examples from practical work.

[Cardiotropic activity of synthetic peptide CH3CO-Lys-Lys-Arg-Arg-NH2 (protectin)].

Peptide CH3CO-Lys-Lys-Arg-Arg-NH2 (protectin) was synthesized and its activity was studied on the model of experimental myocardial infarction in rats in comparison to the reference antihypoxant drug riboxin. Intranasal injections ofprotectin at doses within 2-20 microg/kg once a day by course of 7 days produced a pronounced anti-ischemic action, improved coronary circulation of the blood, increases contractile activity of myocardium, reduced intensity of lipid peroxidation, and improved antioxidant protection. In some respects (improved coronary circulation of the blood, increased antioxidant protection), protectin was more effective than riboxin.

Anticoagulant effects of thioanalogs of thrombin-binding DNA-aptamer and their stability in the plasma.

In order to create effective therapeutically significant oligonucleotide structures, a series of analogs of thrombin-binding aptamer d(GGTTGGTGTGGTTGG) containing thiophosphoryl substitutions were synthesized. The anticoagulation effects of the resultant thrombin-binding aptamer analogs were evaluated and the effects of local thiomodifications on their structure and function were studied, including the effects on stability in blood plasma and resistance to DNA nucleases. A promising modified oligonucleotide (LL11) was found with the structure modified only in TT loops. It retains antithrombin properties of thrombin-binding aptamer, but is more resistant to biodegradation.

Significance of methods for purification of oligodeoxyribonucleotide probes for the efficiency of gene diagnosis by real-time PCR.

Analysis of the use of real-time PCR with fluorescent registration of results for gene diagnosis of infectious diseases showed that the sensitivity and reliability of quantitative evaluation of DNA targets directly depended on the method of purification of oligonucleotide probes. Chromatographic behavior of synthetic probes carrying various fluorophores and fluorescence quenchers was analyzed. Approaches to optimization of purification methods are proposed enabling elimination of previously undetectable admixtures. The importance of these studies is explained by the need in extending the armory of methods for the development and production of diagnosticums for detection of infectious and hereditary diseases, identification of genetically modified organisms, and for a wide spectrum of research in molecular biology and medicine.

[Adolescents' physical development in a poor environmental area].

Physical and sexual developments were determined in 285 schoolchildren aged 12 to 17 years from the town of Karabash, an area of ecological ill-being in the environmental levels of heavy metal salts. The atmospheric air pollution was in parallel monitored at route observational stations. It was found that 39% of the schoolchildren had disharmonic physical development; of them a fourth had lower body weight and decreased chest circumference with normal growth indices. The girls were observed to have a high frequency of a microsomatotype of harmonic physical development and disharmonic physical development mainly at the expense of underweight (52.9% of all the disharmonically developed girls) as compared with the boys. There was a preponderance of female adolescents with sexual retardation. In the population of Karabash girls, the mean age at menarche was 12 years and 9 months +/- 1.5 months.

[Morphologic and morphometric characteristics of the femoral head in experimental necrosis and after incomplete occlusion of the femoral artery]. / Morfologicheskaia i morfometricheskaia kharakteristika golovki bedrennoi kosti pri ee éksperimental'nom nekroze i nepolnoi okkliuzii bedrennoi arterii.

Partial occlusion (by 70-80%) of the femoral artery (FA) below its bifurcation with the deep femoral one was created in 15 dogs 6 months after modeling of aseptic necrosis of femoral head (FH). The dynamics of local circulation was evaluated using the methods of hydrogen clearance, angiography, flowmetry, polarography and mingography. FA and neighboring vessels as well as FH bone tissue were studied using histological, histochemical and morphometric methods. It was found that partial occlusion of FA below its bifurcation with the deep femoral branch resulted after 180-240 days in a redistribution of blood flow in favor of the latter along with a formation of collateral vessel widening as well as in the change in the circulation vector in the direction of the hip joint. This contributed to FH revascularization after modeling of its traumatic aseptic necrosis. The results of the morphological analysis indicate the activation of osteogenesis and gradual replacement of the necrotic area in FH with a newly formed osseous tissue and are suggestive of possible application of this method for clinical use.

[Electroclinical characteristics of Landau-Kleffner syndrome]. / Elektroklinicheskaia kharakteristika sindroma Landau-Kleffnera.

The study aimed at investigating epileptic attack's semiology and other electroclinical characteristics in Landau-Kleffner syndrome as well as therapeutic efficacy. Six patients with Landau--Kleffner syndrome, 5 boys, 1 girl, aged 6-10 years, mean age 7.5 years, have been analyzed. Epileptic attacks were observed only in 3 patients with debut at the age of 2.5-6 years (mean 4 years). In 50% of the cases, the attacks were not detected. The types of epileptic attacks were specified as follows: atypical absences--3 patients; pharyngo-oral--2; secondary generalized--2; atonic falls--1; hemiconvulsive--1. In routine EEG study, regional epileptiform activity was observed in all the patients, being localized in central temporal (3 cases), posterior temporal (1) and fronto-temporal (1) leads. In 3 cases (50%), diffusive epiactivity was also detected. During sleep, emergence of prolonged diffuse epiactivity was revealed for all the patients, with appearance of electrical status epilepticus during slow sleep in 50%. Valproates in dosage 30-60 mg/kg daily were highly effective for stopping epileptic seizures. Significant improvement of speech functions was observed only if antiepileptics sulthiame (ospolot) or clobasam (frizium) were used in addition to basic therapy. Clobasam in dosage 0.5-0.75 mg/kg daily was the most efficient in blockade of EEG diffuse epileptiform activity, reduction of aphasia symptoms and behavior improvement.

[Transport of ions in mitochondria in connection with osmotic concentration of media]. / Peredvizhenie ionov v mitokhondriiakh v sviazi s kontsentratsiei osmotika v srede.

Studies on mitochondria has revealed apparent violation of laws of osmosis, apparently, related to ion transport. In this context, we studied changes in the content of potassium, sodium, magnesium, and calcium in mitochondria from wheat (Triticum aestivum L.) roots incubated in the buffer without the substrate with 0.3 or 0.5 M sucrose as well as potassium, and phosphate. The most pronounced changes were observed for potassium. Potassium arrival to mitochondria was more active at 0.5 than 0.3 M sucrose. The direction of the cation transport depended on its content in the initial buffer. At the certain threshold level, the inflow was replaced with the outflow; this threshold was lower at 0.3 than 0.5 M sucrose. Magnesium was also released from mitochondria; its stable outflow was primarily observed at its lower initial content in the suspension at 0.3 rather than 0.5 M sucrose. The obtained data demonstrated that the apparent violation of laws of osmosis was false and resulted from ion transport. Passive ion transport as a possible mechanism of adaptation to osmotic properties of the external medium is discussed.

[Mitochondria respiration in developing sunflower seeds]. / Dykhanie mitokhondrii razvivaiushchikhsia semian podsolnechnika.

We studied the oxidative and phosphorylative activity of mitochondria in the seeds of three sunflower cultivars (Polevik, Peredovik, and Yubileinyi) during development of the seed embryo within 1 to 54 days after flowering. The rates of succinate oxidation by the mitochondria were 1.5-2 times those of malate or alpha-ketoglutarate oxidation. The ratio of substrate oxidation rates underwent changes during the seed growth. The differences were recorded between cultivars as concerns the times when the maximum oxidation rates were reached. Oxidation was coupled with phosphorylation during the entire period of seed development: the value of respiratory control after Chang changed from 1.4 to 7. By the time of transition to maturation, the rates of oxidation of both substrates and the values of respiratory control and ADP/O decreased. The results we obtained suggest that by days 13-15 of seed embryo growth, the rate of ATP production decreases upon oxidation of Krebs cycle products.

Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1alpha and 1beta following stimulation with heat-inactivated Brucella abortus.

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in both CD4(+) and CD8(+) T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit beta-chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted beta-chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-gamma neutralizing antibodies. Among purified T cells, macrophage inflammatory protein 1alpha and 1beta (MIP-1alpha and MIP-1beta, respectively) secretion was observed primarily in human CD8(+) T cells. The kinetics of beta-chemokine induction in T cells were slow (3 to 4 days). The majority of beta-chemokine-producing CD8(+) T cells also produced IFN-gamma following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8(+) T cells contained stored MIP-1beta that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-1alpha and MIP-1beta production in elutriated monocytes and even higher levels in macrophages. In these cells, beta-chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte- and macrophage-derived beta-chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo.

Immunity and protection against Brucella abortus.

Brucella abortus is an intracellular pathogen that causes disease in cattle and in humans. The response against B. abortus involves the whole gamut of the immune system, from innate to adaptive immunity resulting from stimulation of antigen-presenting cells, NK cells, CD4(+) and CD8(+) T cells, and B cells.

Interferon gamma and interleukin 6 modulate the susceptibility of macrophages to human immunodeficiency virus type 1 infection.

The effect of interferon gamma (IFN-gamma) and interleukin 6 (IL-6) on infection of macrophages with human immunodeficiency virus type 1 (HIV-1) was investigated. By using a polymerase chain reaction-based viral entry assay and viral infectivity assay, it was demonstrated that IL-6 and IFN-gamma augmented susceptibility of monocyte-derived macrophages (MDMs) to infection with T-cell tropic CXCR4-utilizing (X4) HIV-1 strains. Consistent with this finding, IFN-gamma and IL-6 augmented fusion of MDMs with T-tropic envelope-expressing cells. The enhanced fusion of cytokine-treated MDMs with T-tropic envelopes was inhibited by the CXCR4 ligand, SDF-1, and by T22 peptide. IFN-gamma and IL-6 did not affect expression of surface CXCR4 or SDF-1-induced Ca(++) flux in MDMs. In contrast to the effect of IFN-gamma on the infection of MDMs with X4 strains, IFN-gamma inhibited viral entry and productive infection of MDMs with macrophage-tropic (M-tropic) HIV-1. Consistent with this finding, IFN-gamma induced a decrease in fusion with M-tropic envelopes that correlated with a modest reduction in surface CCR5 and CD4 on MDMs. It was further demonstrated that macrophage inflammatory protein (MIP)-1alpha and MIP-beta secreted by cytokine-treated MDMs augmented their fusion with T-tropic-expressing cells and inhibited their fusion with M-tropic envelope-expressing cells. These data indicate that proinflammatory cytokines, which are produced during opportunistic infections or sexually transmitted diseases, may predispose macrophages to infection with X4 strains that, in turn, could accelerate disease progression.

CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor.

To determine whether human immunodeficiency virus type 1 (HIV-1) coreceptors besides CXCR4 and CCR5 are involved in HIV-1 infection of the thymus, we focused on CCR8, a receptor for the chemokine I-309, because of its high expression in the thymus. Similar levels of CCR8 mRNA were detected in immature and mature primary human thymocytes. Consistent with this, [(125)I]I-309 was shown to bind specifically and with similar affinity to the surface of immature and mature human thymocytes. Fusion of human thymocytes with cells expressing HIV-1 X4 or X4R5 envelope glycoprotein was inhibited by I-309 in a dose-dependent manner. In addition, I-309 partially inhibited productive infection of human thymocytes by X4, R5, and X4R5 HIV-1 strains. Our data provide the first evidence that CCR8 functions as an HIV-1 coreceptor on primary human cells and suggest that CCR8 may contribute to HIV-1-induced thymic pathogenesis.

CCR9A and CCR9B: two receptors for the chemokine CCL25/TECK/Ck beta-15 that differ in their sensitivities to ligand.

We isolated cDNAs for a chemokine receptor-related protein having the database designation GPR-9-6. Two classes of cDNAs were identified from mRNAs that arose by alternative splicing and that encode receptors that we refer to as CCR9A and CCR9B. CCR9A is predicted to contain 12 additional amino acids at its N terminus as compared with CCR9B. Cells transfected with cDNAs for CCR9A and CCR9B responded to the chemokine CC chemokine ligand 25 (CCL25)/thymus-expressed chemokine (TECK)/chemokine beta-15 (CK beta-15) in assays for both calcium flux and chemotaxis. No other chemokines tested produced responses specific for the cDNA-transfected cells. mRNA for CCR9A/B is expressed predominantly in the thymus, coincident with the expression of CCL25, and highest expression for CCR9A/B among thymocyte subsets was found in CD4+CD8+ cells. mRNAs encoding the A and B forms of the receptor were expressed at a ratio of approximately 10:1 in immortalized T cell lines, in PBMC, and in diverse populations of thymocytes. The EC50 of CCL25 for CCR9A was lower than that for CCR9B, and CCR9A was desensitized by doses of CCL25 that failed to silence CCR9B. CCR9 is the first example of a chemokine receptor in which alternative mRNA splicing leads to proteins of differing activities, providing a mechanism for extending the range of concentrations over which a cell can respond to increments in the concentration of ligand. The study of CCR9A and CCR9B should enhance our understanding of the role of the chemokine system in T cell biology, particularly during the stages of thymocyte development.

Fusion of monocytes and macrophages with HIV-1 correlates with biochemical properties of CXCR4 and CCR5.

Human macrophages can be infected more efficiently by M-tropic than by T-tropic HIV-1 strains, despite surface expression of both CXCR4 and CCR5 co-receptors. Western blot analyses of total cell extracts and surface proteins from multiple sets of monocytes and macrophages demonstrated substantial differences between CXCR4 molecules. CXCR4 was mainly a monomer in monocytes, but was mainly a species of higher molecular weight (90 kDa) on the surface of macrophages. CCR5 was monomeric in both cell types. A constitutive association between CD4 and the co-receptors was seen in monocytes and macrophages. However, CD4 co-precipitated with CCR5 and CXCR4 monomers, but not with the high-molecular-weight forms of CXCR4, indicating that the high-molecular-weight CXCR4 species in macrophages are not available for association with CD4, which may contribute to the inefficient entry of T-tropic strains into mature macrophages.