[Hybrid revascularization in a patient with Covid-19 and chronic limb ischemia stage IV]. / Gibridnaya revaskulyarizatsiya u patsienta s COVID-19, khronicheskoi ishemiei nizhnei konechnosti IV stepeni.

The authors report hybrid treatment of a patient with angina pectoris class II, multiple previous reconstructive interventions on the aortofemoral segment and chronic ischemia of the left lower limb stage IV and concomitant COVID-19. Coronary angiography was performed after regression of infectious disease under antiviral therapy. Occlusion of the left anterior descending artery was observed that required LAD stenting. On the next day, hybrid revascularization of the lower extremities was implemented: thrombectomy and endarterectomy from the branch of the aorto-femoral bypass graft and deep femoral artery at the first stage, stenting of the orifice of proximal branch of aorto-femoral bypass graft at the second stage, endarterectomy from superficial femoral artery, recanalization and stenting of superficial femoral artery and popliteal artery at the third stage and prosthetic- femoral bypass with autologous vein at the fourth stage. Postoperative angiography revealed patent stents and no residual stenoses. The choice in favor of these procedures and step-by-step approach has been substantiated. The authors emphasized effectiveness and safety of this treatment strategy.

3D Models of Cellular Spheroids As a Universal Tool for Studying the Cytotoxic Properties of Anticancer Compounds In Vitro.

The aim of this work is to develop a 3D cell culture model based on cell spheroids for predicting the functional activity of various compounds in vivo. Agarose gel molds were made using 3D printing. The solidified agarose gel is a matrix consisting of nine low-adhesive U-shaped microwells of 2.3 × 3.3 mm for 3D cell spheroid formation and growth. This matrix is placed into a single well of a 12-well plate. The effectiveness of the cell culture method was demonstrated using human ovarian carcinoma SKOVip-kat cells stably expressing the red fluorescent protein Katushka in the cytoplasm and overexpressing the membrane-associated tumor marker HER2. The SKOVip-kat cell spheroids were visualized by fluorescence microscopy. The cell concentration required for the formation of same-shape and same-size spheroids with tight intercellular contacts was optimized. To verify the developed model, the cytotoxicity of the targeted immunotoxin anti-HER2 consisting of the anti-HER2 scaffold DARP 9_29 and a fragment of the Pseudomonas aeroginosa exotoxin, DARP-LoPE, was studied in 2D and 3D SKOVip-kat cell cultures. The existence of a difference in the cytotoxic properties of DARP-LoPE between the 2D and 3D cultures has been demonstrated: the IC50 value in the 3D culture is an order of magnitude higher than that in the monolayer culture. The present work describes a universal tool for 3D cultivation of mammalian cells based on reusable agarose gel molds that allows for reproducible formation of multicellular spheroids with tight contacts for molecular and cell biology studies.

[Vertebral artery stenosis - surgical, endovascular or hybrid treatment strategy?] / Stenoz pozvonochnoi arterii ­ khirurgicheskaya, endovaskulyarnaya ili gibridnaya strategiya lecheniya?

The main idea of this literature review is based on the uncertainty in the current recommendations regarding the treatment of patients with vertebrobasilar insufficiency (VBI) caused by the presence of hemodynamically significant stenosis of the vertebral artery (VA). The authors present comparative results of medical, endovascular, open surgical methods of treatment, demonstrating the advantages and disadvantages of each of them, describe new hybrid correction options with substantiation of their effectiveness and safety. The results of treatment of patients with VBI without VA stenosis, with atherosclerotic lesions of the internal carotid arteries are presented. The role of carotid endarterectomy in these conditions has been substantiated. Rare cases of VBI caused by abnormal origin of VA from atherosclerotically changed common carotid artery are demonstrated. The treatment options for patients with combined hemodynamically significant stenosis of the VA and carotid arteries are described. The emphasis is made on the need to stratify the risk of complications in this cohort of patients using modern programs to implement a personalized approach to treatment.

[The experience of using drug Afalaza for treatment of lower urinary symptoms in treatment-nave patients with benign prostatic hyperplasia].

INTRODUCTION: Benign prostatic hyperplasia (BPH) is one of the most common diseases in men over 50 years. The prevalence of the BPH increases with age, and pathologic features of BPH are found in about 90% of men over 80 years. AIM: The aim of the study was to study the efficacy and safety of Afalaza for the treatment of lower urinary tract symptoms (LUTS) in treatment-nave patients with BPH. MATERIALS AND METHODS: A multicenter study of using Afalaza for the treatment of LUTS in treatment-nave patients with BPH was carried out in 9 urological centers in Moscow. A total of 80 treatment-nave patients with BPH were enrolled. The improvement in the total score of IPSS, IIEF-5 and QoL after 30 weeks of therapy was evaluated as well as changes in prostate volume and maximum urinary flow rate (Qmax). RESULTS: After 30 weeks of therapy, there was a significant decrease in the total IPSS score. A decrease in the total IPSS score by 5.5 points (+37.9%) from 14.5+/-4.0 at the baseline to 9.0+/-4.1 at the visit 9 was seen. The QoL decreased by 1.8 (-38.3%) points from 4.7+/-1.0 at the baseline. The Qmax also changed from 12.7+/-4.6 to 16.4+/-5.7 (+28.3%) after 30 weeks of therapy. At the visit 9, the total IIEF5 score increased by 3.4+/-4.4 (+19.9%) from 17.1+/-4.3 at the baseline. In addition, prostate volume decreased from 42.7+/-11.1 at baseline to 41.0+/-9.8 cc post-treatment (-5.15%). A reduction of post-void residual urine volume from 26.0+/-25.3 at baseline to 17.7+/-24.2 (-31.9%) post-treatment was also shown. CONCLUSION: The results of a multicenter study demonstrate the efficacy of Afalaza for treatment of treatment-nave patients with LUTS/BPH. Afalaza reduces prostate volume and improves an erectile function.

[Nuclear activation analytical methods and X-ray fluorescence analysis in application to determination of pollutants and trace elements in food and for studying biokinetics of nanoparticles].

For assurance of food quality and safety, it is necessary to control routes of food pollutants, including toxic trace elements in all stages of handling, ranging from the production of agricultural products, including the processing, storage, transportation, and ending with cooking and consumption. For this control the nuclear activation analytical methods (NAAMs) and X-ray fluorescence analysis (XRFA) are studied and developed for the detection of chemical elements in different environments. NAAMs involve two stages: the activation of nuclear isotopes with thermal neutrons or fast charged particles and gamma spectrometry. XRFA technique is based on detecting characteristic fluorescent X-rays of elements. Interest in these methods is due to the relative simplicity of the analysis, the ability to provide the required sensitivity and accuracy of detection of chemical elements. The main objective of the research work is to demonstrate the potential of these techniques for controlling the quality and safety of food products and for research of trace elements' biokinetics with achieving the required accuracy (no worse than 15%) and sensitivity (below the permissible concentrations of harmful substances) and to prepare them for the practical application. Both methods complement each other in terms of expanding the list of detected chemical elements and choosing the best option in the analysis depending on the type of the test sample and readiness of technical means. In addition to the analysis of NAAMs and XRFA capabilities two different but partly connected research options were performed using NAAMs: 1) control of food quality and safety; 2) research of biokinetics of nanoparticles (NPs), incoming with food and water into laboratory animals with special attention to overcoming biological barriers. One of the important result is the demonstration of overcoming the blood/brain barrier by silver NPs when they are ingested into the animals with food or water, and possibility of their accumulation in brains with extremely low excretion (≈6% per month).

A novel bioartificial liver containing small tissue fragments: efficiency in the treatment of acute hepatic failure induced by carbon tetrachloride in rats.

The efficiency of a new bioartificial liver (BAL) containing small tissue fragments in the treatment of acute hepatic failure induced by carbon tetrachloride in rats was evaluated. A day after injection (i.p.) of CCl4 the animals were connected to a BAL containing liver fragments (fragment BAL) and a BAL containing no liver fragments (no-fragment BAL), and extracorporeal hemoperfusion was carried out for 4 h. The activities of alanine transaminase and lactate dehydrogenase as well as the concentrations of ammonia, glucose, urea, and amino acids in plasma were measured. A tendency to the stabilisation of ammonia, glucose, phenylalanine, tyrosine, and other amino acids was revealed at the end of hemoperfusion in poisoned rats connected to the fragment BAL. A statistically significant difference in survival between the animals connected to the fragment BAL and no-fragment BAL was found. The results obtained indicate that the bioreactor containing small liver fragments is effective in the treatment of acute hepatic failure in animals.

Size-dependent optical spectroscopy of a homologous series of CdSe cluster molecules.

The optical properties and electronic structure of a homologous series of CdSe cluster molecules covering a size range between 0.7 and 2 nm are investigated. CdSe cluster molecules with 4, 8 10, 17, and 32 Cd atoms, capped by selenophenol ligands, were crystallized from solution and their structures determined by single-crystal X-ray diffraction. The cluster molecules are composed of a combination of adamanthane and barylene-like cages, the building blocks of the zinc blende and the wurtzite structures of the bulk CdSe. The onset of the room temperature absorption and low-temperature photoluminescence excitation spectra exhibit a systematic blue shift with reduced cluster size manifesting the quantum confinement effect down to the molecular limit of the bulk semiconductor. Blue-green emission, shifted substantially to lower energy from the absorption onset, is observed only at low temperature and its position is nearly independent of cluster size. The wavelength dependence of both photoluminescence and photoluminescence excitation was measured. The emission is assigned to forbidden transitions involving the cluster-molecule surface-capping ligands. This assignment is supported by the emission decay which exhibits distributed kinetics with microsecond time scale. The temperature dependence of the emission intensity is quantitatively explained by multiphonon-induced nonradiative relaxation mediated by low-frequency vibrations of the selenophenol capping ligands. Upon irradiation, the emission of all cluster molecules is quenched. Warming up and recooling leads to recovery of the emission (partial or complete) for all but the cluster molecule with 10 Cd atoms. This temporary darkening is assigned to the photoinduced charging of the cluster-molecule surface ligands, resembling the reversible on-off blinking of the emission observed for larger CdSe nanocrystals.

DIROM: an experimental design interactive system for directed mutagenesis and nucleic acids engineering.

A computer system DIROM for oligonucleotide-directed mutagenesis and artificial gene design has been designed for better experimental planning and control. DIROM permits searching for optimal oligonucleotides with respect to certain important parameters, namely sufficient energy of oligonucleotide-target hybridization, the secondary structure of oligonucleotide and target DNA, the presence of alternate binding sites in the target DNA and terminal G/C pairs. It can also be used to plan polymerase chain reaction experiments, for optimal primer selection, in sequencing, etc. DIROM enables one to search for both existing and potential restriction sites, to perform vector + target sequence construction. The system consists of a set of original algorithms that formalize the empirical knowledge of oligonucleotide action as primers.

Stimulation by calcium chloride of virus-induced interferon formation by blood, haemopoietic organ and continuous human cells.

Calcium chloride stimulated virus-induced production of leukocyte interferon by human and animal blood and haemopoietic organ cells. CaCl2 treatment of surviving cells (leukocytes, human and mouse bone marrow) and Namalva cells was the most effective when carried out simultaneously with adsorption of the virus-inducer or when CaCl2 pretreatment was combines with its subsequent addition together with the virus-inducer. Optimal CaCl2 concentrations were 5 mM for human bone marrow cells and 10 mM for human leukocytes and mouse bone marrow cells. CaCl2 treatment was equivalent to priming in case of interferon induction in human leukocytes and, as distinct from priming, it considerably increased virus-induced interferon production by Namalva cells.

Relationship between the blood concentration of the drug and its cumulative effect: a pharmacokinetic analysis of the nephrotoxic action of gentamicin and streptomycin.

The general principle of dependence of cumulative effects on drug concentration in the blood is proposed. The registered response is regarded as a result of the dual effect of drug blood level and duration of action. The corresponding experimental design consists in maintaining the serum concentration values at several definite levels and determining the response values for each of them. The constant serum level of the drug could be achieved by means of continuous infusion calculated according to the pharmacokinetic model. This principle was proved in the acute experiments on cats which established a relationship between the nephrotoxic effect of gentamicin and streptomycin on the one hand and their concentration in the serum and duration of action on the other.

Translation by bacterial cells of messenger RNA for interferon of animal origin.

Escherichia coli, strain AB 1157, cells are capable of translating human, mouse, and chicken messenter RNA for interferon with production of interferon of the corresponding specifity. This translation occurs in the presence of serum. The activity of the resulting interferon decreased in parallel to dilution of the original mRNA preparation, upon multiple ulitization of the mRNA solution, as well as upon reduction of the interferon- producing activity of cells-donors of mRNA due to prolonged storage of the cells. Unlike animal cells, the bacteria do not require pre-treatment with actinomycin D. The interferon translated by bacteria is inactivated by trypsin and resistant to ribonuclease.

Relationship between the neuromuscular blocking effect of gentamicin and streptomycin and their concentration in blood.

The principle of the analysis of concentration-response relationships is valid in the case if the effective course is defined by a logistic function and the drug distribution is approximated by a two-compartment model. The method of calculation the data to construct the curves describing the dependence of the effect on drug concentration in the central and in peripheral compartments was elaborated. The relations between the concentrations of gentamicin and streptomycin and their peripheral neuromuscular blocking effect were investigated experimentally on cats. The blocking action of both drugs is evident at concentrations higher than the drug serum levels after administration of therapeutic doses, gentamicin being more active.

Mason-Pfizer virus characterization: a similar virus in a human amniotic cell line.

Mason-Pfizer monkey virus (MP-MV) is a RNA virus with an RNA-instructed DNA polymerase first isolated from a rhesus monkey mammary adenocarcinoma in 1970. Until recently, there have been no other isolates. A continuous human amnion cell line, AO, was found to be producing a virus indistinguishable or closely related to the Mason-Pfizer virus as measured by morphological, immunological, and biochemical methods. By thin-section electron microscopy, the extracellular virus particle in AO line is 115 to 130 nm in diameter and has a preformed nucleoid (80 to 90 nm) before budding, properties which are also characteristic of MP-MV. Two proteins of the virus from the AO line were studied. By immunodiffusion, sera which react specifically with MP-MV give a line of identity with virus from the AO line. The AO viral RNA-instructed DNA polymerase purified by phosphocellulose chromatography was specifically inhibited by anti-MP-MV polymerase sera, and the AO cells contained both DNA and RNA sequences related to MP-MV (3)H-DNA. Viruses thus far indistinguishable from MP-MV have also recently been found by others in different human lines, raising again the question of the species of origin of MP-MV. Because the virus in the AO cells cannot be differentiated from MP-MV, we attempted to determine the origin of MP-MV virus by measuring DNA sequences related to MP-MV (3)H-DNA in uninfected human and rhesus monkey cells. The quantity of MP-MV-like DNA sequences in uninfected primate tissues was found to be much lower than the amount of DNA sequences of murine type-B or type-C viruses in uninfected murine tissues. Thus, it was not possible to determine whether the virus produced by AO cells or MP-MV was of human or monkey origin, or both.