Effect of non-steroidal anti-inflammatory agents on interferon induction]

Nonsteroid antiinflammatory agents (NAIA) such as antipyrine, butadion, acetylsalicylic acid, sodium salicylate, stampyrine and 4-iodantipyrine are not interferonogenic. Still, they stimulated interferonogenic action of poly(G).poly(C) in studies on animals. Relation between the interferon-stimulating action of the NAIA and their effect on activity of prostaglandin and the influence on the immune system was suggested.     

Probing the MVAI methyltransferase region that interacts with DNA: affinity labeling with the dialdehyde-containing DNA duplexes

Affinity labeling of methyltransferase MvaI by DNA duplexes containing oxidized 2'-O-beta-D-ribofuranosylcytidine or 1-beta-D-galactopyranosyl)thymine residues was performed. Partial chemical hydrolysis of the covalently bound methylase in the conjugates with the dialdehyde-containing DNA allowed us to determine the amino acid region in the C terminus of methylase MvaI that interacts with DNA.     

The ecological and medical aspects of the symbiosis between Escherichia coli and man

In this work different variants of the symbiosis of E. coli with a human body are analyzed, and the symbiotic relationships between them are shown to follow the type mutualism, commensalism, parasitism and habitation. The authors emphasize that the multiplicity of variants of bacteria-host relationships is based on the phenotypic polymorphism of E. coli clones (clone lines). Taking into account their ecological (symbiotic) features and biomedical importance, all E. coli clones are divided into 4 groups (clusters): mutualists as nonpathogenic organisms; commensals as potential pathogens (causing extraintestinal E. coli infections); parasites as real pathogens (causing acute intestinal infections); "occasional" symbionts of man. The proposition on the cluster structure of E. coli as a species is formulated.     

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity

Background

Central nervous system (CNS) infection is a nearly universal feature of untreated systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment.

Results

After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral therapy and correlated abundances of identified proteins a) within and between subjects, b) with all other proteins across the entire sample set, and c) with "external" CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson''s) ≤ -0.3 and ≥0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node.

Conclusions

Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.     

Taxonomic spectrum and antibiotic resistance of Enterobacteriaceae isolated from bile of patients with cholangitis]

The data on the taxonomic structure and antibiotic resistance of Enterobacteriaceae isolated from bile of patients with various clinical variants of cholangitis are presented. It was shown that bacteriocholia was registered in 53.3-90.9% of the patients during operations and in 88.9-100% of the patients during the postoperative period. Among bilicultures enterobacteria dominated (93.4% of the cases) with predominance of E. coli and Klebsiella spp. (the total about 70%). The enterobacteria isolates were frequently resistant to ampicillin and amoxycillin/clavulanate (92.6 and 70.4% of the strains respectively), gentamicin and amikacin (74.1 and 22.2%), cefazolin and cefotaxime (88.9 and 37.0%). The resistance to imipenem and ciprofloxacin (7.4%) was rare, that should be considered while prescribing drugs for empirical antimicrobial chemotherapy.     

AVPR1A variant associated with preschoolers' lower altruistic behavior

The genetic origins of altruism, defined here as a costly act aimed to benefit non-kin individuals, have not been examined in young children. However, previous findings concerning adults pointed at the arginine vasopressin receptor 1A (AVPR1A) gene as a possible candidate. AVPR1A has been associated with a range of behaviors including aggressive, affiliative and altruistic phenotypes, and recently a specific allele (327 bp) of one of its promoter region polymorphisms (RS3) has been singled out in particular. We modeled altruistic behavior in preschoolers using a laboratory-based economic paradigm, a modified dictator game (DG), and tested for association between DG allocations and the RS3 "target allele." Using both population and family-based analyses we show a significant link between lower allocations and the RS3 "target allele," associating it, for the first time, with a lower proclivity toward altruistic behavior in children. This finding helps further the understanding of the intricate mechanisms underlying early altruistic behavior.     

Calix[4]arene methylenebisphosphonic acids as inhibitors of fibrin polymerization

Calix[4]arenes bearing two or four methylenebisphosphonic acid groups at the macrocyclic upper rim have been studied with respect to their effects on fibrin polymerization. The most potent inhibitor proved to be calix[4]arene tetrakis-methylene-bis-phosphonic acid (C-192), in which case the maximum rate of fibrin polymerization in the fibrinogen + thrombin reaction decreased by 50% at concentrations of 0.52 × 10(-6) M (IC(50)). At this concentration, the molar ratio of the compound to fibrinogen was 1.7 : 1. For the case of desAABB fibrin polymerization, the IC(50) was 1.26 × 10(-6) M at a molar ratio of C-192 to fibrin monomer of 4 : 1. Dipropoxycalix[4]arene bis-methylene-bis-phosphonic acid (C-98) inhibited fibrin desAABB polymerization with an IC(50) = 1.31 × 10(-4) M. We hypothesized that C-192 blocks fibrin formation by combining with polymerization site 'A' (Aα17-19), which ordinarily initiates protofibril formation in a 'knob-hole' manner. This suggestion was confirmed by an HPLC assay, which showed a host-guest inclusion complex of C-192 with the synthetic peptide Gly-Pro-Arg-Pro, an analogue of site 'A'. Further confirmation that the inhibitor was acting at the initial step of the reaction was obtained by electron microscopy, with no evidence of protofibril formation being evident. Calixarene C-192 also doubled both the prothrombin time and the activated partial thromboplastin time in normal human blood plasma at concentrations of 7.13 × 10(-5) M and 1.10 × 10(-5) M, respectively. These experiments demonstrate that C-192 is a specific inhibitor of fibrin polymerization and blood coagulation and can be used for the design of a new class of antithrombotic agents.     

Detection of infectious agents in heart valves during endocarditis using PCR technique

Infectious endocarditis can be caused by various microorganisms. Diagnostics of local infection by microbiological methods is not always effective. For that reason we performed a study aimed for direct detection of potential infectious agents by polymerase chain reaction in patients' heart valve tissue. DNA of infectious agents was revealed in 72% of heart valve tissue samples from patients with septic endocarditis; in studied samples, along with bacterial DNA, herpesviruses' DNA was detected. Obtained results confirm the presence of infection, which allows to perform specific diagnostics of infectious complications after implantation of prosthetic cardiac valves.