Parameters of Ionic and Acid-Base Balance during Assist Circulation with a LVAD Disc Pump.

In chronic experiments on calves, the effect of the left-ventricular assist device (LVAD) technique by using a disc pump on the indicators of ionic and acid-base homeostasis. At blood velocity of 20% from the total volume, a trend towards an increase in K+ concentration and a slight decrease in the concentration of Na+, pH, and standard base excess in animal plasma were observed. If the blood velocity increased up to 90%, the indicators of ionic and acid-base homeostasis returned to their baseline values. In parallel, stroke volume and cardiac output as well as BP at the outlet of the heart and inside it and HR increased simultaneously with a blood pressure decrease in the input cannula site. There were no differences in plasma concentrations of Ca2+ and Cl- at different blood flow volumes.

[Morphological changes in rabbit cornea after implantation of a new keratoprosthesis supporting plate]. / Morfologicheskie izmeneniya rogovitsy krolika pri implantatsii novoi modeli opornoi plastinki keratoproteza.

PURPOSE: To evaluate biocompatibility of the new keratoprosthesis supporting plates (KSP) in rabbits in vivo. MATERIAL AND METHODS: The study included 15 chinchilla rabbits. In the first group (5 rabbit eyes) KSP made of hydrophobic acryl with square penetrating holes of 220×220 micron (model 1) were inserted into rabbits' corneas. In the second group (5 eyes), KSP made of hydrophobic acryl were used that had trapezoidal fenestrations with size (from 170×130 micron to 180×70 microns) gradually changing from periphery to the center of KSP (model 2). The control group rabbits (5 eyes) had 1/2 of Fyodorov-Zuev KSP made of titanium implanted. All animals were observed for up to 3 months with biomicroscopy and optical coherence tomography of the anterior segment. The animals were then euthanized and had their corneo-scleral discs excised and then examined with optical microscopy and scanning electron microscopy (SEM). RESULTS: After 3 months, there was only one case of KSP protrusion in the first group. In the second group, thinning of the corneal layers above the central part of KSP occurred in one case. The presence of polymer KSP (of both models) in the corneal stroma was found not to cause formation of rough fibrotic tissue. At the same time, adhered cellular and fibrous elements were discovered on the surface and inside the holes of the polymer KSP, while on the surface of the titanium plate cellular elements were absent. CONCLUSION: Supporting plates made of hydrophobic acrylic material can potentially serve as a foundation for the new keratoprosthesis design.

[Exhaled Breath Analysis in Diagnostics of Cardiovascular Diseases].

Exhaled breath analysis is a novel tool for diagnostics of different diseases. Taking into account the secretory function of the lungs, the composition of exhaled breath is different in physiological and pathological conditions. In this review we consider of some substances which content vary in cardiovascular diseases - pentane, isoprene, carbon monoxide and trimethylamine. Modern technologies allow to move the analysis of exhaled breath from research laboratories into clinical practice. Thus, a new tool for real time of screening various cardiovascular diseases has appeared in the arsenal of physicians.

Advances in the Application of Modified Nucleotides in SELEX Technology.

Aptamers are widely used as molecular recognition elements for detecting and blocking functional biological molecules. Since the common "alphabet" of DNA and RNA consists of only four letters, the chemical diversity of aptamers is less than the diversity of protein recognition elements built of 20 amino acids. Chemical modification of nucleotides enlarges the potential of DNA/RNA aptamers. This review describes the latest achievements in a variety of approaches to aptamers selection with an extended genetic alphabet.

Evolution of catalytic centers of antibodies by virtual screening of broad repertoire of mutants using supercomputer.

It is proposed to perform quantum mechanical/molecular dynamics calculations of chemical reactions that are planned to be catalyzed by antibodies and then conduct a virtual screening of the library of potential antibody mutants to select an optimal biocatalyst. We tested the effectiveness of this approach by the example of hydrolysis of organophosphorus toxicant paraoxon using kinetic approaches and X-ray analysis of the antibody biocatalyst designed de novo.

ANESTHETIC MANAGEMENT OF DELIVERY IN PATIENTS WITH COMPLEMENT-ASSOCIATED DISORDERS. CLINICAL OBSERVATION OF A PREGNANT WOMAN WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.

There was a case in MRRIOG (Moscow Regional Research Institute of Obstetrics and Gynecology) in 2015 when pregnant patient with paroxysmal nocturnal hemoglobinuria(PNH) has successfully passed through a delivery process. This paper analyzes the medical history, clinical, laboratory and instrumental examination, particularly anesthesia tactics for the patients with complement-associated diseases during delivery. The presented clinical case demonstrates the need for and the importance of early diagnosis of PNH in pregnant women. Of course, women with PNH are one of the most complex contingent ofpregnant women, threatened by the development of obstetric and anesthetic complications, and it requires constant monitoring of clinical and laboratory parameters of their condition, the joint hematologist, obstetri- cian and anesthesiologist observationand delivery in hospitals of III and IV levels.

[Proton Transfer Reaction Mass Spectrometry of Exhaled Breath in Diagnostics of Heart Failure].

BACKGROUND: Exhaled breath analysis is one of directions in the search for novel biomarkers of chronic heart failure (CHF). According.

Molecular Dynamics Investigation of a Mechanism of Allosteric Signal Transmission in Ribosomes.

The ribosome is a molecular machine that synthesizes all cellular proteins via translation of genetic information encoded in polynucleotide chain of messenger RNA. Transition between different stages of the ribosome working cycle is strictly coordinated by changes in structure and mutual position both of subunits of the ribosome and its ligands. Therein, information regarding structural transformations is transmitted between functional centers of the ribosome through specific signals. Usually, functional centers of ribosomes are located at a distance reaching up to several tens of angstroms, and it is believed that such signals are transduced allosterically. In our study, we attempted to answer the question of how allosteric signal can be transmitted from one of the so-called sensory elements of ribosomal tunnel (RT) to the peptidyl transferase center (PTC). A segment of RT wall from the E. coli ribosome composed of nucleotide residues A2058, A2059, m(2)A2503, G2061, A2062, and C2063 of its 23S rRNA was examined by molecular dynamics simulations. It was found that a potential signal transduction pathway A2058-C2063 acted as a dynamic ensemble of interdependent conformational states, wherein cascade-like changes can occur. It was assumed that structural rearrangement in the A2058-C2063 RT segment results in reversible inactivation of PTC due to a strong stacking contact between functionally important U2585 residue of the PTC and nucleotide residue C2063. A potential role for the observed conformational transition in the A2058-C2063 segment for regulating ribosome activity is discussed.

[Technological Perspectives in Developing Carbon Nanotube-based DNA-modified Biosensors].

In this research we investigated the response of DNA-modified carbon nanotubes in the presence of thrombin and albumin. We analyzed aptamer-carbon nanotube interactions by Raman spectroscopy and by analyzing resistance after each step of biosensor assembly. We have shown that intensity of G-band decreases due to interconnection of aptamer and carbon nanotube and this also evaluates in decrease of sensor structure resistance. The response of the sensor exposed to thrombin and albumin differs essentially from each other. This fact serves as the prerequisite for the development of a highly selective biosensor. Results of this investigation can be used in creation of new generation of personal health monitoring systems.

PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).

[Surgical treatment of pregnant women with benign ovarian tumors].

The article describes the features of surgery in tumors and tumor-like formations of the ovaries in pregnant women. The influence of surgery on the course and outcome of pregnancy and childbirth is presented. It is showed high efficiency of laparoscopic surgery during I and II trimesters of pregnancy.

[Endovascular closure of iatrogenic arteriovenous anastomosis of the iliac artery and vein].

The presented herein clinical case report concerns successful endovascular closure of a iatrogenic lesion of the iliac artery and inferior vena cava with formation of a pathological arteriovenous anastomosis manifesting itself by venous thromboembolic syndrome and severe right-ventricular insufficiency.

Aptamer RA36 inhibits of human, rabbit, and rat plasma coagulation activated with thrombin or snake venom coagulases.

RA36 DNA aptamer is a direct anticoagulant prolonging clotting time of human, rabbit, and rat plasma in the thrombin time test. Anticoagulant activity of RA36 is lower than that of recombinant hirudin. During inhibition of human plasma clotting activated with echitox (coagulase from Echis multisquamatus venom), the aptamer presumably binds to meisothrombin exosite I. The sensitivity of human plasma to the aptamer 5-fold surpasses that of rat plasma. Analysis of RA36 binding to coagulase of Agkistrodon halys venom (ancistron) is required for proving the effect of aptamer on polymerization of human fibrinogen.

[Pathology diagnostics by human breath analyze].

Modern medicine experiences deficit of inexpensive rapid screening technologies despite progress in the development of diagnostic methods for various diseases. A promising approach is the analysis of exhaled air known to contain thousands of volatile organic substances whose composition differs considerably in health and disease. We isolated certain compounds that may be used as biomarkers of cardiovascular pathology (nitric oxide, carbon monoxide, pentane, isoprene, acetone). There is a variety of methods for the detection of substances in the exhaled air; such as gas spectrography, mass spectrometry, etc. However, ion mobility spectrometry appears the most suitable technique for the purpose of screening studies due to its high speed and sensitivity, small size of the apparatus, and possibility to measure trace amounts of the substances of interest. Possibilities to diagnose lung cancer based on exhaled air composition are considered.

PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (PDBe) (http://www.ebi.ac.uk/pdbe/) is actively working with its Worldwide Protein Data Bank partners to enhance the quality and consistency of the international archive of bio-macromolecular structure data, the Protein Data Bank (PDB). PDBe also works closely with its collaborators at the European Bioinformatics Institute and the scientific community around the world to enhance its databases and services by adding curated and actively maintained derived data to the existing structural data in the PDB. We have developed a new database infrastructure based on the remediated PDB archive data and a specially designed database for storing information on interactions between proteins and bound molecules. The group has developed new services that allow users to carry out simple textual queries or more complex 3D structure-based queries. The newly designed 'PDBeView Atlas pages' provide an overview of an individual PDB entry in a user-friendly layout and serve as a starting point to further explore the information available in the PDBe database. PDBe's active involvement with the X-ray crystallography, Nuclear Magnetic Resonance spectroscopy and cryo-Electron Microscopy communities have resulted in improved tools for structure deposition and analysis.

[Comparative in vitro study of anticoagulant activity of RA36 DNA aptamer in human, rabbit, and rat blood plasma].

DNA aptamer RA36 with a molecular weight of 10000 is direct-acting anticoagulant whose efficacy is lower than that of recombinant hirudin and unfractionated heparin (UFH) in blood clotting time (BCT), activated blood recalcification time (ABRT), recalcification time (RT), prothrombin time (PT), and activated partial thromboplastin time (APTT) tests. The anticoagulant effect of RA36 is comparable with that of UFH in the thrombin time (TT) test, but is lower than the effect of recombinant hirudin. Analysis of the blood and plasma anticoagulant activity during intravenous bolus administration of aptamer RA36 in rabbits and rats is based on the use ABRT (in blood case) and APTT/RT (in plasma case) tests. The range of doses for evaluation of pharmacodynamic parameters of RA36 during intravenous bolus administration in rabbits and rats is 3 - 34 mg/kg and 1 - 27 mg/kg, respectively. Accordingly, designed dose range for humans is 1 -29 mg/kg.

Water replacement hypothesis in atomic details: effect of trehalose on the structure of single dehydrated POPC bilayers.

We present molecular dynamics (MD) simulations to study the plausibility of the water replacement hypothesis (WRH) from the viewpoint of structural chemistry. A total of 256 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) lipids were modeled for 400 ns at 11.7 or 5.4 waters/lipid. To obtain a single dehydrated bilayer relevant to the WRH, simulations were performed in the NP(xy)h(z)T ensemble with h(z) > 8 nm, allowing interactions between lipids in the membrane plane and preventing interactions between neighboring membranes via periodic boundary conditions. This setup resulted in a stable single bilayer in (or near) the gel state. Trehalose caused a concentration-dependent increase of the area per lipid (APL) accompanied by fluidizing the bilayer core. This mechanism has been suggested by the WRH. However, dehydrated bilayers in the presence of trehalose were not structurally identical to fully hydrated bilayers. The headgroup vector was in a more parallel orientation in dehydrated bilayers with respect to the bilayer plane and maintained this orientation in the presence of trehalose in spite of APL increase. The total dipole potential changed sign in dehydrated bilayers and remained slightly positive in the presence of trehalose. The model of a dehydrated bilayer presented here allows the study of the mechanisms of membrane protection against desiccation by different compounds.

Comparison of models of thrombin-binding 15-mer DNA aptamer by molecular dynamics simulation.

Two models of 15-mer thrombin-binding DNA aptamer (15TGT) were comparatively analyzed by molecular dynamics simulation using the GROMACS software package. The two original models of 15TGT were obtained by NMR and X-ray analyses. The models significantly differ in the topology of loops and the direction of oligodeoxyribonucleotide chain. The evolution of the two structures in parm99 force fields and parmbsc0 optimized for nucleic acids was analyzed in our adaptation of GROMACS architecture. It is shown that the best system for description of the 15TGT structure is the model obtained by X-ray analysis in the parmbsc0 force field.

Mapping the ribosomal protein S7 regulatory binding site on mRNA of the E. coli streptomycin operon.

In this work it is shown by deletion analysis that an intercistronic region (ICR) approximately 80 nucleotides in length is necessary for interaction with recombinant E. coli S7 protein (r6hEcoS7). A model is proposed for the interaction of S7 with two ICR sites-region of hairpin bifurcations and Shine-Dalgarno sequence of cistron S7. A de novo RNA binding site for heterologous S7 protein of Thermus thermophilus (r6hTthS7) was constructed by selection of a combinatorial RNA library based on E. coli ICR: it has only a single supposed protein recognition site in the region of bifurcation. The SERW technique was used for selection of two intercistronic RNA libraries in which five nucleotides of a double-stranded region, adjacent to the bifurcation, had the randomized sequence. One library contained an authentic AG (-82/-20) pair, while in the other this pair was replaced by AU. A serwamer capable of specific binding to r6hTthS7 was selected; it appeared to be the RNA68 mutant with eight nucleotide mutations. The serwamer binds to r6hTthS7 with the same affinity as homologous authentic ICR of str mRNA binds to r6hEcoS7; apparent dissociation constants are 89 +/- 43 and 50 +/- 24 nM, respectively.

[Trans-translation: facts and hypothesis].

Trans-translation is a unique process which switches the synthesis of a polypeptide chain encoded by a nonstop messenger RNA to the mRNA-like domain of tmRNA. It is used in bacterial cells for rescuing the ribosomes arrested during translation of nonstop mRNA and directing this mRNA and the product polypeptide for degradation. tmRNA activity is essential for bacterial survival under adverse conditions, quality-control of translation and regulation of certain physiological pathways. This review will focus on recent advances in trans-translation investigation: the details of tmRNA-SmpB interaction and the structure of the early ribosomal complexes will be characterized; the causes for the empty A site appearance in the translating ribosomes, possible mechanisms of the stalled ribosomes recognition and resume codon determination will be discussed, the proteins degraded nonstop mRNA and tagged peptide will be viewed.