[Prognostic factors in patients with hematological malignancies and concomitant chronic hepatitis C].

The study evaluated the impact of HCV infection on the prognosis in patients with hematological malignancies. A total of 96 patients with anti-HCV antibodies were enrolled, with the age of 37.8 (3.0-81.0) years old, 39.6% had non-Hodgkin's lymphoma. Chronic hepatitis C (CHC) was diagnosed in 46.9% patients prior to malignancy development, in 38.5% patients simultaneously with malignancy, and in 14.6% patients during malignancy treatment. Clinical and biochemical signs of HCH were mild in most of the patients, minimal liver fibrosis (F0-1 by METAVIR system) was discovered in 47.3% patients, severe fibrosis or cirrhosis (F3-4) was diagnosed in 40% of participants. Only 20 (20.8%) of patients received antiviral therapy against HCV prior to enrollment. Regression analysis demonstrated that age >55 years old, late onset of antiviral therapy, and poor nutritional status were significant predictors of death from hematological malignancy. Survey conducted among physicians of hematological oncology hospitals in Saint-Petersburg revealed gaps in knowledge on presentation and risks of HCV infection, as well as on opportunities of modern antiviral therapy.

[Disorders of carbohydrate-lipid metabolism and galectin-3 level as factors of liver fibrosis progression in chronic hepatitis C].

AIM: To assess the effect of metabolic disorders and galectin-3 levels on the progression of liver fibrosis in chronic hepatitis C. MATERIALS AND METHODS: 106 patients with HCV without decompensated liver cirrhosis were examined. EXCLUSION CRITERIA: age younger than 20 and older than 65 years, diabetes, coronary heart disease, hypertension, alcoholism, drug addiction. Laboratory examination (biochemical blood test, enzyme immunoassay (ELISA) with determination of HCV-Ab antibodies, viral load) was supplemented with liver elastometry (Fibroscan) with fibrosis assessment (kPa, METAVIR scale). The body mass index of Quetelet (kg/m2), the presence of abdominal obesity, insulin resistance were evaluated. Serum levels of insulin and galectin-3 were determined by ELISA. RESULTS: In 45% of patients, an increase in ITM was revealed, in 44% abdominal obesity, in 62% insulin resistance. In 75% abdominal obesity was determined in patients with liver fibrosis F3F4. Insulin resistance was found more often in patients with fibrosis F01 56.7%. Significant correlations between the level of galectin-3 and the degree of liver fibrosis (in kPa) [r=0,206, p=0,034], as well as the stage of liver fibrosis (on the METAVIR scale) [r=0,247, p=0,01] were obtained. The level of galectin-3 in liver cirrhosis was 6.32 (4.57; 9.64) ng/ml, which is significantly higher than in F0 3.96 (1.45; 5.30) ng/ml (p=0.002) and F1 3.85 (2.20; 5.83) ng/ml (p=0.002). By calculating the specificity and sensitivity of isolated for F4 stage of liver fibrosis (ROC-curve, the level of galectin-3 is 5.21 ng/ml), the level of specificity of 74.7%, sensitivity of 74% was established. CONCLUSION: We found a significant relationship between the disturbances of carbohydrate-lipid metabolism and liver fibrosis, the level of galectin-3 and fibrosis stage of the liver. The prognostic value of increasing the level of galectin-3 for predicting the cirrhotic stage of liver fibrosis is substantiated.

[POSSIBILITY OF USING NESTED POLYMERASE CHAIN REACTION FOR DIAGNOS- TICS OF DISEASES CAUSED BY VARICELLA ZOSTER VIRUS].

AIM: Demonstrate the possibility of using nested PCR method for determination of Varicella Zoster virus (VZV) in clinical samples of peripheral blood of patients. MATERIALS AND METHODS: Material from 35 patients with clinical manifestations of herpes zoster and control group of 20 healthy donors was used in the study. Monocyte fraction of venous blood cells, pretreated with heparin, was isolated by centrifugation in ficoll-verografin density gradient, total DNA was then isolated from cells by phenol-chloroform extraction with subsequent precipitation with alcohol. Polymerase chain reaction was carried out in thermocyclers Tercyc and TProfessional Gradient (Biometra), amplified DNA was analyzed by electrophoresis on 1.6% agarose gel in the presence of ethidium bromide. RESULTS: Data on detection of viral DNA in blood monocytes in 17 (49%) of ill patients, as well as in 1 (out of 20 in control group) practically healthy donor were obtained. A possibility of a subclinical reactivation of the virus is discussed in the latter case. CONCLUSION: A possibility of viral DNA determination in monocytes of patient blood without using expensive equipment is shown, that could find application in clinical practice, especially for diagnostics of patients with non-characteristic clinical manifestations, as well as patients with subclinical forms of the disease.

[Markers of endothelial dysfunction (VCAM-1 and vWF) in chronic hepatitis C].

UNLABELLED: AIM. To estimate the blood levels of endothelial factors (soluble vascular adhesion molecule 1 (sVCAM-1) and von Willebrand factor (vWF:Ag)) in relation to the magnitude of the biochemical, histological, and virological characteristics of chronic hepatitis C (CHC). SUBJECTS AND METHODS: The investigation enrolled 69 patients with asymptomatic CHC. The mean age of the examined was 33.6 +/- 7.8 years. Laboratory examination included a standard set of clinical and biochemical parameters for chronic hepatitides. The stage of hepatic fibrosis (HF) and the degree of histological activity were determined by the METAVIR scale based on histological examination of liver biopsy specimens, by using the calculated FibroTest (BioPredictive, France) and indirect ultrasonic liver elastometric assay (Fibroscan). The serum content of sVCAM-1 and vWF:Ag were measured by ELISA. RESULTS: Elevated sVCAM-1 and/or vWF:Ag levels were found in 33.3% of the patients with CHC. There was a significantly higher increase in blood sVCAM-1 levels in patients with cytolytic syndrome than in those with normal alanine aminotransferase activity. Particularly high sVCAM-1 levels (more than twice higher) were recorded in the CHC patients with severe HF (F3-F4) than in those with milder HF (F0-F2) (1966.98 (1299.79, 3451.73) and 975.98 (888.94, 1226.13) ng/ml (p < 0.001). There were higher blood levels of vWF:Ag in the patients with severe HF (F3-F4) than in those with early-stage HF (FO-F2)--1.61 (1.29; 1.81) and 1.31 (1.15, 1.45) U/ml; p < 0.05). CONCLUSION: In the patients with HCH, the found elevated blood sVCAM-1 and vWF:Ag levels related to the biochemical activity of hepatitis and, to a greater extent, with the degree of HF can judge the implication of endothelial dysfunction in the pathogenesis of chronic HCV infection.

[Hepatoprotective activity of remaxol in patients with chronic hepatic disorders].

This milticentre randomized clinical study of the efficiency of remaxol infusion solution (hepatoprotective medicine for chronic liver dysfunction) included 494 patients with chronic hepatitis B and C. 294 of them staying in 7 clinics were given remaxol and 200 ones received placebo. Randomization was achieved by the envelope method. A detailed description of clinical and laboratory characteristics of the diseases is presented. Effects of remaxol vs placebo on the functional activity of affected liver are discussed. Results of laboratory and clinical analysis indicate that mechanism of remaxol action is based on hepatoprotective, antioxidative, and anticholestatic activities of the drug.

[Developmental disorders of academic skills in children: the efficacy and safety of Tenoten for children in the multicenter double-blind placebo-controlled randomized study]. / Narusheniya razvitiya uchebnykh navykov u detei: effektivnost' i bezopasnost' Tenotena detskogo po dannym mnogotsentrovogo dvoinogo slepogo platsebo-kontroliruemogo randomizirovannogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of tenoten for children in the treatment of specific developmental disorders of academic skills in children of 1-3 grades. MATERIAL AND METHODS: Two hundred and forty children, aged 7-9 years, (Total set, Safety population) with verified specific reading disorder (F81.0), specific spelling disorder (F81.1), specific disorder of arithmetical skills (F81.2), mixed disorder of scholastic skills (F81.3; F81.2+F81.0, or F81.2+F81.1, or F81.2+F81.0+F81.1), diagnosed with the use of logopedic or psychological testing (15-35 scores in Fotekova T.A. and Akhutina T.V. reading and writing tests; 5-15 scores in arithmetical subscale of the Wechsler Intelligence Scale for Children) were enrolled in the study. CT was conducted in 10 clinical centers in Russian Federation in 2015- 2019. Patients were randomized into two groups. The first one (n=122) received tenoten for children in a dose of 1 tablet 3 times a day, the second one (n=118) was administered placebo in the same dosage regimen. The clinical data on 237 children (121 of the tenoten group and 116 of the placebo group) were used for Intention-to-treat efficacy analysis. Data on 220 children (115 of the tenoten group and 105 of the placebo group) were included in Per-protocol analysis. The duration of study was 12 weeks. The mean total academic skills (reading, spelling, and counting) score in groups after 12 weeks of treatment was set as the primary efficacy endpoint. RESULTS: The mean total academic skills score increased by 18.55±15.87 points. The significant total difference between the median changes in the total score in the tenoten and placebo groups was 5 points. There was a trend towards positive changes in reading and spelling mean scores in tests that didn't reach statistical significance due to lack of normal distribution of points in samples. There were 73 adverse events (AEs) in 42 patients of the tenoten group and 95 AEs in 31 children of the placebo group. No serious or severe AEs were registered in the tenoten group. No AEs definitely related to the study treatment were registered. No negative drug interactions were observed in the tenoten group. CONCLUSIONS: Tenoten for children is an effective and safe treatment for specific developmental disorders of academic skills in primary school children. Tenoten for children is well tolerated. The treatment is characterized by a high level of adherence of children and their parents to therapy.

Plasmakristall-4: New complex (dusty) plasma laboratory on board the International Space Station.

New complex-plasma facility, Plasmakristall-4 (PK-4), has been recently commissioned on board the International Space Station. In complex plasmas, the subsystem of µm-sized microparticles immersed in low-pressure weakly ionized gas-discharge plasmas becomes strongly coupled due to the high (103-104 e) electric charge on the microparticle surface. The microparticle subsystem of complex plasmas is available for the observation at the kinetic level, which makes complex plasmas appropriate for particle-resolved modeling of classical condensed matter phenomena. The main purpose of PK-4 is the investigation of flowing complex plasmas. To generate plasma, PK-4 makes use of a classical dc discharge in a glass tube, whose polarity can be switched with the frequency of the order of 100 Hz. This frequency is high enough not to be felt by the relatively heavy microparticles. The duty cycle of the polarity switching can be also varied allowing to vary the drift velocity of the microparticles and (when necessary) to trap them. The facility is equipped with two videocameras and illumination laser for the microparticle imaging, kaleidoscopic plasma glow observation system and minispectrometer for plasma diagnostics and various microparticle manipulation devices (e.g., powerful manipulation laser). Scientific experiments are programmed in the form of scripts written with the help of specially developed C scripting language libraries. PK-4 is mainly operated from the ground (control center CADMOS in Toulouse, France) with the support of the space station crew. Data recorded during the experiments are later on delivered to the ground on the removable hard disk drives and distributed to participating scientists for the detailed analysis.

Antigenic properties of vaccinia virus and of the virus recombinant strains expressing heterologous genes.

Immunologic properties of vaccinia virus (VV), strain LIPV, and VV recombinant strains containing the gene of hepatitis B virus surface antigen and the TK gene of herpes simplex virus (HSV) have been studied. Production of antibodies against the majority of VV structural proteins, including nucleocapsid internal proteins was demonstrated in rabbits. Insertion of heterologous genes into the VV genome was without effect on the spectrum of antibodies produced against VV virion proteins. The data obtained in volunteers indicate that not only virus-neutralizing antibodies but also antibodies against most VV structural proteins are preserved in humans over many years. Reimmunization of volunteers with VV recombinant stimulates synthesis of antibodies against virion proteins whereas the spectrum of antibodies remains unchanged. Humans and rabbits did not differ in the spectrum of antibodies to VV virion proteins.

RNA sequences of opposite polarities transcribed from a large part of vaccinia virus genome are accumulated in the cytoplasm.

Labelled vaccinia virus DNA was used in saturation-hybridization experiments with RNA extracted from virus-infected cells. An excess of "late" cytoplasmic RNA converted 45% of DNA into DNA-RNA hybrids, whereas 17% of DNA could be converted into hybrids by RNA extracted from purified nuclei. RNA-RNA hybrids obtained from cytoplasmic RNA by self-annealing and ribonuclease treatment, were melted and used in hybridization with DNA: 36% of DNA was hybridized at the maximal concentration used.

Biologic properties and genome structure of the recombinants between ectromelia and rabbitpox viruses.

Administration of rabbitpox virus (RPV) DNA, cleaved into 2 fragments by SmaI restrictase, into ectromelia virus (EMV)-infected chick fibroblast cells yielded recombinants whose properties were characteristic of both parents. Some recombinants capable of producing RPV-type lesions upon intracutaneous (i.c.) infection of rabbits could also produce EMV-specific lesions upon footpad inoculation of mice. The analysis of some recombinants as well as vaccinia virus strains has shown that the ability of the virus to reproduce when injected into the mouse footpad is a necessary, but not a sufficient condition for production of EMV-type lesions. According to restrictase analysis of recombinant DNA, the genome of recombinants mainly consists of RPV DNA sequences with insertions of small EMV DNA fragments.

Two vaccinia virus recombinants expressing HBsAg with different concentration of A- and pre-S2 antigenic determinants.

Comparative studies of two vaccinia virus (VV) recombinants expressing the hepatitis B virus (HBV) surface antigen (HBsAg) including the pre-S2 region (M-protein) showed that the L-pre-S2/15 recombinant expressed 5-fold more HBsAg as determined by the content of a-determinant than the recombinant v137. However, both recombinants expressed comparable amounts of the pre-S2 antigenic determinant as assessed by enzyme immunoassay with monoclonal antibodies. According to our calculations, one HBsAg unit expressed by the recombinant v137 contained 7-9 times more pre-S2 antigen than did one HBsAg unit expressed by the L-pre-S2/15 recombinant. Binding of pre-S2 region to polymerized human serum albumin was shown not to be an efficient assay at low pre-S2 concentration. HBsAg expressed by the v137 recombinant was less extensively secreted from cells as compared to that expressed by L-pre-S2/15 recombinant. Both recombinants induced the production of antibodies to the pre-S2 antigenic determinant in rabbits. L-pre-S2/15 induced anti-HBsAg a-determinant antibody as well.

[Analysis of vaccinia virus genome with restriction endonucleases EcoRI, BamHI, KpnI and HindIII]. / Ispol'zovanie restriktaz EcoRI, BamHI, KpnI i HindIII dlia analiza genoma virusa ospovaktsiny.

Restriction endonucleases EcoRI, BamHI, Hind III and KpnI were used for analysis of acccinia virus DNA. The number and size of restriction endonuclease fragments were determined by gel electrophoresis and the analysis of 3H-labeled vaccinia virus DNA. It was shown that many EcoRI and BamHI fragments had the same and similar sizes. The exact number of EcoRI and BamHI fragments were estimated only after analysis of [3H]-labeled vaccinia DNA. The vaccinia genome sizes calculated from HindIII, KpnI and EcoRI are very close to the actual genome weight. But the sum of BamHI fragments is much lower than those determined by electron microscope method.

[Physical mapping of DNA-temperature-sensitive mutations of vaccinia virus]. / Fizicheskoe kartirovanie DNK-temperaturochuvstvitel'nykh mutatsii virusa ospovaktsiny.

Four DNA-temperature-sensitive (ts) mutations were mapped in the genome of vaccinia virus (VV). Physical mapping of these mutations was performed by restriction analysis of the genomes of recombinants between VV DNA- ts mutants and ectromelia virus as well as by the marker rescue with cloned restriction fragments of VV DNA. One of the mutations was mapped on the HindIII-E-fragment. Biochemical studies of this mutant indicate that the mutation is not in the DNA polymerase gene which is located on the same fragment. The other three mutations were mapped in a 10 kilobase region in the middle of the HindIII-D-fragment. As shown previously, these mutations inactivate different genes, and the products of these genes participate directly in the DNA synthesis. Thus, at least three proteins involved in the VV DNA synthesis are encoded by neighboring genes in the central part of the viral genome.

[Insertion mutants of the vaccinia virus. The effect of inactivating E7R and D8L genes on the biological properties of the virus]. / Insertsionnye mutanty virusa ospovaktsiny. Vliianie inaktivatsii genov E7R i D8L na biologicheskie svoistva virusa.

The integrative plasmids with the expressive marker gene for beta-galactosidase were constructed for insertional inactivation of nonessential genes E7R and D8L of vaccinia virus located in the central region of the viral genome. Inactivation of the D8L gene in the strains WR and LIVP results in smaller viral plaques in the culture of chicken embryo cells, decreases the viral ability to propagate in mouse brain and has no effect on the size and character of damage in intracutaneous infection of rabbits. Inactivation of E7R gene did not affect the known biological properties of the virus. The existence of the nonessential genes in the central region of the viral genome, inactivation of which does not result in viral attenuation, can be used for increase of antigenic activity of the live attenuated vaccines.

[Changes in the reflex excitability of spinal motor neurons in newborn infants during sleep and increases in environmental temperature]. / Izmenenie reflektornoi vozbudimosti spinal'nykh motoneironov u novorozhdennykh detei vo vremia sna v usloviiakh povyshennoi temperatury okruzhaiushchei sredy.

Reflex excitability of the spinal motor centres was studied in newborns by the monosynaptic testing (H-reflex) method during the rise of air temperature in the cunette up to 32 degrees and 34 degrees as compared to the control data obtained at 30 degrees C. It was shown that at temperatures of 32 degrees and 34 degrees C the reflex excitability of spinal motoneurones is lower than in the control. A narrowing of the range and a weakening of the stimuli were recorded at which the H-reflex could be elicited. The possible ways are discussed in which the surrounding temperature affects reflex excitability of the spinal motor centres.

[Moscow Research Institute of Viral Preparations tissue-culture smallpox vaccine in a coded control experiments of adult revaccination by scarification]. / Izuchenie tkanevoi ospennoi vaktsiny MNIIVP v shifrovannom kontroliruemom opyte pri revaktsinatsii vzroslykh metodom skarifikatsii.

Comparative studies of tissue culture and dermal smallpox vaccines were carried out in a strictly controlled coded trial by revaccination of adults by scarification. Two lots of tissue culture and one lot of dermal vaccines with a similar infectious titer (8.0 lg PFU/ml) were used. All the lots tested "took" in 100%. In the group revaccinated with tissue culture vaccine seroconversion was observed in 94.2 +/- 2.8%--95.0 +/- 2.8%, with a 4.6 +/- 5.3-fold rise in geometric mean antibody titer; the dermal smallpox vaccine produced seroconversion in 85.7 +/- 4.4% with 4.3-fold rise in geometric mean antibody titer. Febrile reactions in revaccines with the tissue culture vaccine were observed in 23.1%--26.1% which did not exceed this parameter in the group revaccinated with the dermal vaccine (25.2%); in all the groups febrile ractions were of mild degree (37.1 degrees--38 degrees C). Local reactions of the type of confluent erythema were observed 1.8--5.3-fold more frequently among those revaccinated with the dermal vaccine than among those revaccinated with the tissue culture vaccine. Thus, the tissue culture vaccine used epicutaneously was as good as the dermal one by the take rate and antigenic activity, but had less remarked reactogenic properties which allows to recommend it for public health practice.

[RNA transcripts of both strands of viral DNA in cells infected with vaccinia virus]. / RNK-transkripty obeikh nitei virusnykh DNK v kletkakh, zarazhennykh virusom ospovaktsiny.

Denaturated 3H-thymidine-labeled vaccinia virus DNA was hybridized with an excess of "late" virus-specific RNA isolated from virus-infected chick embryo cell cultures 8 hours postinfection. The percentage of DNA converted into DNA-RNA hybrid under these conditions never exceeded 50%. If the RNA preparation had been self-annealed prior to hybridization, the percentage was decreased slightly. On the other hand, if the self-annealed RNA had been treated with RN-ase and the double-stranded DNA-RNA hybrids had been denaturated, they became capable of converting into hybrids at least 68% of the labeled DNA. These data indicate that transcription of both DNA strands occurs in a large portion (over 68%) of vaccinia virus genome.

[Study of the properties of a tissue smallpox vaccine manufactured by the Moscow Research Institute of Viral Preparations]. / Izuchenie svoistv tkanevoi ospennoi vaktsiny proizvodstva Moskovskogo nauchno-issledovatel'skogo instituta virusnykh preparatov.

The tissue culture vaccine against smallpox has some important advantages over the dermal preparation: it is free from bacterial contamination, contains no serum proteins, and suitable for intradermal inoculation with jet injections. The virus for the tissue culture smallpox vaccine is grown in Japanese quail embryo cultures controlled for the absence of contaminating viruses. In trials of the tissue culture smallpox vaccine in 800 revaccinated volunteers no untoward reactions or complications were observed. The antigenic activity of the tissue culture smallpox vaccine was superior to that of dermal vaccine used in the same dose: the geometric mean neutralizing antibody titre after vaccination with the tissue and dermal preparations was 1 : 256 and 1 : 158, respectively, and the antibody rise was 4.5- and 2.5-fold.

[Verification of the safety, inoculability, reactogenicity and antigenic properties of a live recombinant smallpox-hepatitis B vaccine in an experiment in volunteers]. / Proverka bezopasnosti, privivaemosti, reaktogennosti i antigennykh svoistv zhivoi rekombinantnoi ospenno-gepatitnoi B-vaktsiny v opyte ne dobrovol'tsakh.

Trials of the first Soviet live recombinant smallpox-hepatitis B vaccine (SHBV) in volunteers (20 men aged 18-20 years) showed its safety, good "take"-rate, and lower reactogenicity as compared with the standard smallpox vaccine (LIVP strain). Smallpox virus-neutralizing antibodies in response to SHBV were produced as well as in response to the smallpox vaccine. Revaccination of human subjects with smallpox vaccine and SHBV 45 days after the previous vaccination resulted in antibody booster to vaccinia virus. After two inoculations of SHBV at an interval of 45 days no anti-HBsAg antibodies were found for 3 months after the last vaccination. However, even a single vaccination with SHBV induced priming to HBsAg. This could be demonstrated after inoculation of the subjects vaccinated with SHBV with one dose of plasma hepatitis vaccine. In the subjects vaccinated with SHBV antibody in response to the plasma vaccine formed more frequently and in higher titres than in those prevaccinated with smallpox vaccine or placebo.

[Intensity of the peroxidation of membrane lipids and metabolism of lymphocytes in viral hepatitis patients]. / Intensivnost' perekisnogo okisleniia lipidov membran i metabolizm limfotsitov u bol'nykh virusnymi gepatitami.

Patients with acute viral hepatitis B were found to have an increase in the processes of peroxidization of lymphocyte membrane lipids and in the activity of superoxide dismutase, an antioxidant enzyme, depending on the period of the disease and its severity. Patients with a severe form of the disease were found to have specific features of the intracellular metabolism of lymphocytes in comparison with patients having moderate forms of the disease. To a lesser degree, the characteristics of lymphocytes in hepatitis cases depended of the etiology of the disease, caused by hepatitis virus B, C or the combination of both. The properties of lymphocytes were found to reflect the immune reactiveness of the body and could be used for evaluating the severity of the disease, prognostication and the achievement of convalescence.