[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.

[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.

[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.

Measurement of the interaction force among particles in three-dimensional plasma clusters.

The interaction forces between particles have been studied in a 3D plasma cluster under weak external confinement. A suitable combination of dc and rf applied to a small electrode provided gravity compensation, uniform over dimensions much larger than the cluster itself. The forces acting on the particles could be reconstructed due to unique three-dimensional diagnostics, which allow us to obtain coordinates and velocities of all the particles simultaneously. The measurements yield a maximum (external) confinement force of 1.4 x 10(-15)N and interparticle force that is repulsive at short distances and attractive at larger distances, with a maximum attractive force of 2.4 X 10(-14)N at particle separation 195 microm.

Co-morbidity of infectious and addictive diseases in St. Petersburg and the Leningrad Region, Russia.

The Russian health care system is organized around specific diseases, with relatively little focus on integration across specialties to address co-morbidities. This organizational structure presents new challenges in the context of the recent epidemics of injection drug use (IDU) and HIV. This paper uses existing and new data to examine the prevalence of reported new cases of drug dependence (heroin) and HIV over time as well as associations between drug dependence and alcoholism, hepatitis B and C, and tuberculosis in the City of St. Petersburg and the Leningrad region. We found a sharp rise in reported cases of IDU beginning in 1991 and continuing until 2002/2003, followed by a sharp rise in newly reported cases of HIV. These rises were followed by a drop in new cases of HIV and drug addiction in 2002/2003 and a drop in the proportion of HIV-positive individuals with IDU as a risk factor. Infection with hepatitis B and C were common, especially among injection drug users (38 and 85%, respectively), but also in alcoholics (7 and 14%). Tuberculosis was more common in alcoholics (53%) than in persons with alcoholism and drug dependence (10%), or with drug dependence alone (4%). Though these data have many limitations, they clearly demonstrate that drug dependence and/or alcoholism, HIV, hepatitis, and tuberculosis frequently co-occur in St. Petersburg and the Leningrad Region. Prevention and treatment services across medical specialties should be integrated to address the wide range of issues that are associated with these co-morbidities.

Diagnostics of the electronegative plasma sheath at low pressures using microparticles.

Levitated particles are a new powerful diagnostic of the midplasma sheath region. They can reveal features undetectable either to plasma or to surface measurements. The equilibrium position of microparticles suspended in an oxygen plasma sheath, together with a model of the levitation force and Langmuir probe measurements, gives evidence of secondary electropositive plasmas in the already established plasma sheath, in the range of parameters where the modified Bohm criterion breaks down into multiple solutions.

[The assessment of the course of an infectious process by the membrane status of the peripheral blood lymphocytes]. / Otsenka techeniia infektsionnogo protsessa po sostoianiiu membran limfotsitov perifericheskoi krovi.

Lipid peroxidation in lymphocyte membranes is studied in patients with acute viral hepatitis B and B + C and in chronic alcoholics with Flexner's dysentery and with uneventful premorbid history. The intensity of lipid peroxidation in lymphocytes was increased, corresponding to the severity and period of infection. The premorbid background and therapy influenced the lymphocyte membrane status, which can serve as an integral indicator of immunological reactivity of the organism.

[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.

[Characteristics of viral hepatitis in addicts with consideration of lymphocyte membrane condition]. / Kharakteristika virusnykh gepatitiov u narkomanov s uchetom sostoianiiamembran limfotsitov.

AIM: To study changes in the condition of lymphocyte membranes of patients with acute viral hepatitis B (AVHB) in narcotic addicts. MATERIALS AND METHODS: 136 patients with AVHB have been examined for endogenic intoxication (plasma levels of middle-size molecular peptides, urine levels of red cells). 74% of the examinees had practiced parenteral injections of opium substitutes. Measurements were made of lymphocyte levels of malonic dialdehyde and superoxide dismutase activity characterizing free radical lipid peroxidation, enzymes of the main metabolic cycles. RESULTS: AVHB addicts often display antibodies to hepatitis C virus, high indices of endogenic intoxication. CONCLUSION: Viral hepatitis was associated with enhanced intensity of lymphocyte membrane lipid peroxidation correlating with the disease severity and duration irrespective of concomitant drug addiction. Early convalescence in drug addicts ran with persisting metabolic disturbances in the immunocompetent cells. This is a pathogenetic sign of the disease transformation to the chronic form.

[The isolation and characteristics of a chemically modified allergen (allergoid) from Dermatophagoides pteronyssinus mites]. / Poluchenie i kharakteristika khimicheski modifitsirovannogo allergena (allergoida) iz kleshchei Dermatophagoides pteronyssinus.

Chemically modified allergens (allergoids) were obtained from house dust mites (Dermatophagoides pteronyssinus). The allergenicity of allergoids in comparison with commercial mite allergen was determined by the skin prick test and by the in vitro test of degranulation of passively sensitized rat mast cells. Changes in allergoid molecules were determined with the use of gel filtration in a column packed with Sephadex G-75, isoelectric focusing in polyacrylamide gel, the determination of the concentration of end amino groups and the enzymatic activity of preparations, as well as HPLC. The possibility of using these methods for controlling the process of modification was studied. The results confirmed the fact that the modification on the allergenic preparation really occurred and the allergenic activity of allergoids was low.

[The biochemical aspects of the pathogenesis of viral hepatitides]. / Biokhimicheskie aspekty patogeneza virusnykh gepatitov.

502 patients with acute viral hepatitis B were examined for blood levels of hydrocortisone and insulin, blood proteolytic systems, proteinase inhibitors, acute phase proteins. Most of the biochemical reactions promoted compensation and adaptation processes inhibiting the disease progression. In severe and progressive hepatitides biochemical mechanisms of adaptation are impaired. This entails pathogenetic implications.

[The significance of lipid peroxidation in the pathogenesis of leptospirosis and its complications]. / Znachenie perekisnogo okisleniia lipidov v patogeneze leptospiroza i ego oslozhnenii.

Lipid peroxidation (LPO) and antioxidant plasma activity were evaluated in 39 patients with leptospiral jaundice. At the height of the disease LPO proceeded more actively, being the highest in cases of severe complications. Early in the disease course general antioxidant activity of plasma was inhibited significantly more noticeably in complicated versus uncomplicated leptospirosis. This confirms pathogenetic implication of membrane LPO in leptospirosis. The approaches to prognostication of the disease course and completeness of the response are proposed.

[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.

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.