Analysis of Immunobiological Properties of Recombinant Streptococcus pneumoniae Pneumolysin.

We compared the immunogenicity of recombinant S. pneumoniae pneumolysin (rPly) when administered with and without Al(OH) adjuvant, and evaluated the protective properties of recombinant protein in the active defense experiment. It was shown that double immunization with rPly+Al(OH) increases the levels of IgG antibodies in comparison with the control (p<0.

Analysis of Toxicity of Recombinant Pneumolysin from Streptococcus pneumoniae.

We studied toxicity of recombinant Streptococcus pneumoniae pneumolysin protein in experiments on mice and its cytopathogenic effect on cultures of Vero green monkey kidney cells and human lung carcinoma A549 cells in vitro. In vivo and in vitro experiments proved the absence of compromised toxicity and direct cytopathogenic action of the recombinant protein.

Recombinant Pneumolysin of Pneumococci Induces TLR4 Expression and Maturation of Dendritic Cells In Vitro.

Pneumolysin (Ply) is a target for the development of serotype-independent pneumococcal vaccines, an important condition for the efficacy of which is their ability to activate innate immunity with the subsequent formation of adaptive immunity. In this study, the ability of recombinant full-length Ply (rPly) of pneumococci to induce TLR expression and maturation of dendritic cells generated from mouse bone marrow was evaluated. It was shown that rPly in vitro increased the number of dendritic cells expressing Toll-like receptor 4 (TLR4) on the membrane.

Action of the Photochrome Glyght on GABAergic Synaptic Transmission in Mouse Brain Slices.

Glyght is a new photochromic compound described as an effective modulator of glycine receptors at heterologous expression, in brain slices and in zebrafish larvae. Glyght also caused weak inhibition of GABA-mediated currents in a cell line expressing α1/β2/γ2 GABA receptors. However, the effects of Glyght on GABAergic transmission in the brain have not been analysed, which does not allow a sufficiently comprehensive assessment of the effects of the compound on the nervous system.

Simultaneous Monitoring of pH and Chloride (Cl) in Brain Slices of Transgenic Mice.

Optosensorics is the direction of research possessing the possibility of non-invasive monitoring of the concentration of intracellular ions or activity of intracellular components using specific biosensors. In recent years, genetically encoded proteins have been used as effective optosensory means. These probes possess fluorophore groups capable of changing fluorescence when interacting with certain ions or molecules.

Subunit-Specific Photocontrol of Glycine Receptors by Azobenzene-Nitrazepam Photoswitcher.

Photopharmacology is a unique approach that through a combination of photochemistry methods and advanced life science techniques allows the study and control of specific biological processes, ranging from intracellular pathways to brain circuits. Recently, a first photochromic channel blocker of anion-selective GABA receptors, the azobenzene-nitrazepam-based photochromic compound (Azo-NZ1), has been described. In the present study, using patch-clamp technique in heterologous system and in mice brain slices, site-directed mutagenesis and molecular modeling we provide evidence of the interaction of Azo-NZ1 with glycine receptors (GlyRs) and determine the molecular basis of this interaction.

Novel Acetylcholinesterase Inhibitors Based on Uracil Moiety for Possible Treatment of Alzheimer Disease.

In this study, novel derivatives based on 6-methyluracil and condensed uracil were synthesized, namely, 2,4-quinazoline-2,4-dione with ω-(-nitrilebenzylethylamino) alkyl chains at the N atoms of the pyrimidine ring. In this series of synthesized compounds, the polymethylene chains were varied from having tetra- to hexamethylene chains, and secondary NH, tertiary ethylamino, and quaternary ammonium groups were introduced into the chains. The molecular modeling of the compounds indicated that they could function as dual binding site acetylcholinesterase inhibitors, binding to both the peripheral anionic site and active site.

Photocontrol of Endogenous Glycine Receptors In Vivo.

Glycine receptors (GlyRs) are indispensable for maintaining excitatory/inhibitory balance in neuronal circuits that control reflexes and rhythmic motor behaviors. Here we have developed Glyght, a GlyR ligand controlled with light. It is selective over other Cys-loop receptors, is active in vivo, and displays an allosteric mechanism of action.

Immunization with Recombinant Pneumolysin Induces the Production of Antibodies and Protects Mice in a Model of Systemic Infection Caused by Streptococcus pneumoniae.

Immunogenic and protective activity of recombinant pneumolysin was studied in experiments on male BALB/c mice. The mice were immunized intraperitoneally with recombinant pneumolysin sorbed on Al(OH) (200 μg per mouse). In 2 weeks after immunization, the isotypes of antibodies to recombinant pneumolysin in the serum of immunized mice were determined by ELISA.

CLARITY analysis of the Cl/pH sensor expression in the brain of transgenic mice.

Genetically encoded biosensors are widely used in cell biology for the non-invasive imaging of concentrations of ions or the activity of enzymes, to evaluate the distribution of small molecules, proteins and organelles, and to image protein interactions in living cells. These fluorescent molecules can be used either by transient expression in cultured cells or in entire organisms or through stable expression by producing transgenic animals characterized by genetically encoded and heritable biosensors. Using the mouse Thy1 mini-promoter, we generated a line of transgenic mice expressing a genetically encoded sensor for the simultaneous measurements of intracellular Cl and pH.

A photoswitchable GABA receptor channel blocker.

Background And Purpose: Anion-selective Cys-loop receptors (GABA and glycine receptors) provide the main inhibitory drive in the CNS. Both types of receptor operate via chloride-selective ion channels, though with different kinetics, pharmacological profiles, and localization. Disequilibrium in their function leads to a variety of disorders, which are often treated with allosteric modulators.

Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer's Disease.

Background/objective: Alzheimer's disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues.

Developmental Changes in the Inhibition of Glycinergic Synaptic Currents by Niflumic Acid in Hypoglossal Motoneurons.

Mammalian brainstem hypoglossal motoneurones (HMs) receive powerful synaptic glycinergic inputs and are involved in a variety of motor functions, including respiration, chewing, sucking, swallowing, and phonation. During the early postnatal development, subunit composition of chloride-permeable glycine receptors (GlyRs) changes leading to a decrease of "fetal" alpha2 and elevation of "adult" alpha1 GlyR subunits. It has been recently demonstrated that niflumic acid (NFA), a member of the fenamate class of non-steroidal anti-inflammatory drugs, is an efficient subunits-specific blocker of GlyRs.

On symmetries, resonances and photonic crystals in morphogenesis.

Biological symmetries, theories of the morphogenetic field, resonant interactions and the role of photons in morphogenetic processes represented the main fields of interest of Lev Beloussov and his followers. This review article includes some results of our study on the important role of resonances and photonic crystals in genetic informatics. Mathematical formalisms of differential Riemannian geometry and tensor analysis are used for modeling inherited curved surfaces in biomorphology and for understanding conformal bio-symmetries connected with the networks of curvature lines of surfaces.

I-Ching, dyadic groups of binary numbers and the geno-logic coding in living bodies.

The ancient Chinese book I-Ching was written a few thousand years ago. It introduces the system of symbols Yin and Yang (equivalents of 0 and 1). It had a powerful impact on culture, medicine and science of ancient China and several other countries.

Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging.

6-Methyluracil derivatives as acetylcholinesterase inhibitors for treatment of Alzheimer's disease.

Background: Alzheimer's disease (AD) is the major age-related progressive neurodegenerative disorder. The brain of AD patients suffers from loss of cholinergic neurons and decreased number of synapses [1]. AD is caused by an imbalance between Aβ production and clearance, resulting in increased amount of Aβ in various forms [2].

6-Methyluracil Derivatives as Bifunctional Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease.

Novel 6-methyluracil derivatives with ω-(substituted benzylethylamino)alkyl chains at the nitrogen atoms of the pyrimidine ring were designed and synthesized. The numbers of methylene groups in the alkyl chains were varied along with the electron-withdrawing substituents on the benzyl rings. The compounds are mixed-type reversible inhibitors of cholinesterases, and some of them show remarkable selectivity for human acetylcholinesterase (hAChE), with inhibitory potency in the nanomolar range, more than 10,000-fold higher than that for human butyrylcholinesterase (hBuChE).

Platelet inhibition beyond conventional antiplatelet agents: expanding role of angiotensin receptor blockers, statins and selective serotonin reuptake inhibitors.

Aspirin, dipyridamole, cilostazol, thienopyridines and glycoprotein IIb/IIIa inhibitors represent the classical examples of the established antiplatelet agents commonly used for the secondary prevention in patients after vascular events. Obviously, the era of expanding antiplatelet regimens and indications may require new agents as the substitutes, or additions to the available strategies. However, recent results of the majority of antiplatelet trials strongly suggest boarder line advantages in clinical outcomes, and higher associated bleeding risks with the novel antiplatelet agents or/and regimens.

[The role of rheological changes of blood and hemostasis in the development of acute neurosensory hypoacusis].

We studied blood rheology and hemostasis in patients with acute neurosensory hypoacusis (ANH) of different genesis to clarify correlations of these disorders with an ANH form. After examination 72 ANH patients (60 male and 12 female, age 19-68) were divided into three groups by ANH etiology: ANH of vascular genesis (group 1, 47 patients), ANH of viral genesis (group 2, 19 patients), ANH of traumatic genesis (group 3, 6 patients). Blood rheology was studied on viscosimeter Low-Shear 30 (Switzerland); hematocrit--on Autocrit (USA) centrifuge, platelet aggregation--on aggregometer Elvi 840 (Italy), coagulation--on coagulometer Tetra (Spain).

[General anesthesia tools in endovascular surgery of the conductive heart system].

The anesthetic management course was analyzed in 224 patients who underwent nonvascular surgeries on the conductive heart system. Analgesic and anti-stress techniques, which do not affect the intracardial conductivity and ensure the successful outcome of surgery with spontaneous or auxiliary ALV, were designed on the basis of research. The above schemes were introduced in practice with their efficiency being confirmed.

[The accumulation of proteins with chitinase activity in the culture media of the parent and mutant Serratia marcescens strain grown in the presence of mitomycin C].

The study of the accumulation pattern of extracellular proteins with chitinase activity in the parent Serratia marcescens strain Bú 211 (ATCC 9986) grown in the presence of mitomycin C and its mutant strain with the constitutive synthesis of chitinases grown in the absence of the inducer showed that chitinase activity appeared in the culture liquids of both strains at the end of the exponential phase (4 h of growth) and reached a maximum in the stationary phase (18-20 h of growth). The analysis of the culture liquids (12 h of growth) by denaturing electrophoresis in PAAG followed by the protein renaturation step revealed the presence of four extracellular proteins with chitinase activity and molecular masses of 21, 38, 52, and 58 kDa.

[Anesthesiology in the surgical treatment of supraventricular tachyarrhythmias].

Different anesthesias were used in 197 patients operated for supraventricular tachiarrhythmias through a transvenous access. Hypnoanalgesia based on preventive injection of a potent nonnarcotic antiinflammatory agent xefocame (lornoxicame), drip infusion of propofol (2-3 mg/kg/h), and bolus injection of dormicum under conditions of spontaneous respiration proved to be the best method.

[Results of radiation monitoring in Moscow].

The results of assessing the radiation situation due to global fallouts, obtained from measurement of 137Cs and 90Sr in over 400 samples from natural environmental objects in Moscow in 1979-1999 have indicated that the levels of the substances in the atmospheric fallouts are in agreement with the mean Russian levels and the mean annual activity of these radionuclides in the ambient air are 6 orders lower than the allowable values laid down in NRB-99. In Moscow, the mean effective dose of external exposure to natural and cosmogenic radionuclides is no greater than 1 m3v a year. The individual effective doses of internal and external exposures of the population to global fallouts averages 13 mu k3v a year.