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.

Molecular hydrogen in minerals as a clue to interpret ∂D variations in the mantle.

Trace amounts of water dissolved in minerals affect density, viscosity and melting behaviour of the Earth's mantle and play an important role in global tectonics, magmatism and volatile cycle. Water concentrations and the ratios of hydrogen isotopes in the mantle give insight into these processes, as well as into the origin of terrestrial water. Here we show the presence of molecular H2 in minerals (omphacites) from eclogites from the Kaapvaal and Siberian cratons. These omphacites contain both high amounts of H2 (70 to 460 wt. ppm) and OH. Furthermore, their ∂D values increase with dehydration, suggesting a positive H isotope fractionation factor between minerals and H2-bearing fluid, contrary to what is expected in case of isotopic exchange between minerals and H2O-fluids. The possibility of incorporation of large quantities of H as H2 in nominally anhydrous minerals implies that the storage capacity of H in the mantle may have been underestimated, and sheds new light on H isotope variations in mantle magmas and minerals.

[Incidence of postoperative cognitive dysfunction after simultaneous carotid surgery and coronary artery bypass grafting in patients with asymptomatic cerebral atherosclerosis]. / Chastota razvitiia posleoperatsionnoi kognitivnoi disfunktsii posle simul'tannoi operatsii na koronarnykh i vnutrennikh sonnykh arteriiakh pri asimptomnom techenii tserebral'nogo ateroskleroza.

AIM: To evaluate the incidence of early postoperative cognitive dysfunction (POCD) after simultaneous carotid surgery and coronary artery bypass grafting (CABG) in patients with asymptomatic cerebral atherosclerosis. MATERIAL AND METHODS: Fifty-three patients with polyvascular disease and asymptomatic cerebral atherosclerosis undergoing simultaneous unilateral carotid endarterectomy (CEE) and CABG were recruited in the study. Core cognitive functions were assessed with the Mini Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) at days 2-3 before the indexed surgery and at days 7-10 after it. All the patients were assigned to two groups based on the baseline MMSE score: one group with mild cognitive impairment (MCI) and another one without MCI. Neurodynamic measurements were performed using the Status-PF hardware-software complex (certificate #2001610233 of the Russian Agency for Patents and Trademarks), followed by the calculation of the integral indicator of the main cognitive domains according to the corresponding algorithms. Attention, memory and neurodynamics were evaluated in all participants. POCD was diagnosed with a decrease from the initial indicators of memory, attention and neurodynamics by 20% in 20% of the tests. RESULTS: Patients had complications in the early postoperative period, regardless of the presence of MCI. A decline among the core cognitive functions was observed in both groups of patients at days 7-10 after the surgery. Patients demonstrated an increase in the reaction time while performing neurodynamic test battery compared with the baseline values. Alterations in memory and attention were not significant. Significant changes in the integral indicator of cognitive status were determined in both groups of patients. It increased by 14% in patients without MCI (0.34±0.2 in the preoperative period vs. 0.39±0.3 in the postoperative period, p=0.04), and by 36% in patients with MCI (0.25±0.19 vs. 0.39±0.3, p=0.003). Regardless of the presence or absence of MCI, all patients had low cognitive status or even that below the average in the perioperative period. Despite the increase in the average values of cognitive status indicators in the postoperative period, 56% of patients (n=14) without MCI and 71% of patients with MCI (n=20) had early POCD. CONCLUSION: Patients with polyvascular disease, regardless of the presence of MCI, had low cognitive status or even that below the average, probably contributing to the elimination of the expected positive effects of CEE. The absence of MCI at baseline does not guarantee the preservation of cognitive status after surgery. Patients with polyvascular disease after myocardial and cerebral revascularization remain at high risk of exacerbating cognitive impairment, and, therefore, require an individual approach and a reasonable choice of the optimal surgical strategy.

[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.

The Preferable Binding Pose of Canonical Butyrylcholinesterase Substrates Is Unproductive for Echothiophate.

In this paper, we, for the first time, describe the interaction between the butyrylcholinesterase enzyme and echothiophate, a popular model compound and an analogue of the chemical warfare agents VX and VR, at the atomistic level. Competition between the two echothiophate conformations in the active site was found using molecular modeling techniques. The first one is close to the mode of binding of the substrates of choline series (butyrylcholine and butyrylthiocholine) and is inhibitory, since it is unable to react with the enzyme. The second one is characterized by a significantly worse estimated binding affinity and is reactive. Thus, echothiophate combines the features of two types of inhibitors: competitive and suicidal. This observation will help clarify the kinetic reaction scheme in order to accurately assess the kinetic constants, which is especially important when designing new butyrylcholinesterase variants capable of full-cycle hydrolysis of organophosphorus compounds.

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.

[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.

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.

Structural Features of the Telomerase RNA Gene in the Naked Mole Rat Heterocephalus glaber.

Telomere length, an important feature of life span control, is dependent on the activity of telomerase (a key enzyme of the telomere-length-maintaining system). Telomerase RNA is a component of telomerase and, thus, is crucial for its activity. The structures of telomerase RNA genes and their promoter regions were compared for the long-living naked mole rat and different organisms. Two rare polymorphisms in Heterocephalus glaber telomerase RNA (hgTER) were identified: A→G in the first loop of pseudoknot P2b-p3 (an equivalent of 111nt in hTR) and G→A in the scaRNA domain CR7-p8b (an equivalent of 421nt in hTR). Analysis of TER promoter regions allowed us to identify two new transcription factor binding sites. The first one is the ETS family site, which was found to be a conserved element for all the analyzed TER promoters. The second site is unique for the promoter region of TER of the naked mole rat and is a binding site for the SOX17 transcription factor. The absence of one Sp1 site in the TER promoter region of the naked small rat is an additional specific feature of the promoter area of hgTER. Such variation in the hgTER transcription regulation region and hgTER itself could provide increased telomerase activity in stem cells and an extended lifespan to H. glaber.

[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.

Module-activity relationship of G-quadruplex based DNA aptamers for human thrombin.

G-quadruplex based DNA aptamers for human thrombin are promising pharmaceuticals as anticoagulants. Initially discovered 15-mer DNA aptamer (15-TBA) has a minimal G-quadruplex structure which is able to inhibit thrombin. 15-TBA was modified and extended to improve aptamer activity and in vivo stability providing 31-TBA, NU172, RA-36, and some others as successful examples. In this paper an interplay between G-quadruplex (pharmacophore module) and additional modules has been studied. An original turbidimetric assay and conventional coagulation tests were applied to evaluate both inhibitory activity and type of inhibiting for aptamers constructed by exchanging the modules between 31- TBA and NU172. Additional modules strongly affect pharmacophore module inhibitory activity either enhancing or reducing it. RA-36 aptamer has two putative pharmacophore entities which also interplay being functionally non-equal. 5'- truncated RA-36 has half of the activity of RA-36, and the same as for 15-TBA. On the contrary 3'-truncated RA-36 has intermediate activity in between 15-TBA and RA-36. These results indicate fine regulation of G-quadruplex inhibitory activity by additional modules, as well as non-trivial behavior of joined pharmacophore modules.

[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.

DNA aptamers for human thrombin with high anticoagulant activity demonstrate target- and species-specificity.

G-quadruplex-based DNA aptamers for human thrombin represent promising pharmaceuticals having high anticoagulant activity, rapid clearance from the bloodstream, and availability of DNA antidote. High specificity of aptamers minimizes side-effects but at the same time leads to difficulties when choosing animal model for preclinical trials. Well described minimal G-quadruplex 15-TBA, elongated with hinge and duplex regions 31-TBA, and developed recently modular aptamer RA-36 were investigated thoroughly and compared in this paper. To estimate the species-specificity of aptamers the inhibition constants and types were determined for human fibrinogen hydrolysis with human, bovine, porcine, rabbit, rat, and mouse thrombins using turbidimetric assay. Coagulation tests on human fibrinogen, factor II deficient human plasma and animal plasmas were conducted to verify turbidimetric data and reveal either the concentration effects or the influence of other plasma components. And finally, a set of tests on blood clotting cascade was performed to investigate target-specificity of RA-36 aptamer.

Identification of Novel RNA-Protein Contact in Complex of Ribosomal Protein S7 and 3'-Terminal Fragment of 16S rRNA in E. coli.

For prokaryotes in vitro, 16S rRNA and 20 ribosomal proteins are capable of hierarchical self- assembly yielding a 30S ribosomal subunit. The self-assembly is initiated by interactions between 16S rRNA and three key ribosomal proteins: S4, S8, and S7. These proteins also have a regulatory function in the translation of their polycistronic operons recognizing a specific region of mRNA. Therefore, studying the RNA-protein interactions within binary complexes is obligatory for understanding ribosome biogenesis. The non-conventional RNA-protein contact within the binary complex of recombinant ribosomal protein S7 and its 16S rRNA binding site (236 nucleotides) was identified. UV-induced RNA-protein cross-links revealed that S7 cross-links to nucleotide U1321 of 16S rRNA. The careful consideration of the published RNA- protein cross-links for protein S7 within the 30S subunit and their correlation with the X-ray data for the 30S subunit have been performed. The RNA - protein cross-link within the binary complex identified in this study is not the same as the previously found cross-links for a subunit both in a solution, and in acrystal. The structure of the binary RNA-protein complex formed at the initial steps of self-assembly of the small subunit appears to be rearranged during the formation of the final structure of the subunit.