LABORATORY DIAGNOSTICS OF ACTIVE AND LATENT HHV 6-INFECTION IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES.

INTRODUCTION: Human herpes virus type 6 (HHV 6) can cause serious infectious complications in immunodeficient patients. It is also capable of integrating into the genome of the infected cell. Due to this, there can be a misdiagnosis between viral integration and active infection during laboratory diagnostics. Thus, determination of HHV 6 infection using proper laboratory tools is relevant. Also the data on viral interference of HHV 6 and other herpes viruses are very poor especially for patients with hematological malignancies. The aim of the study was to identify laboratory markers of HHV 6 and the form of infection in patients with hematological malignancies. MATERIALS AND METHODS: 98 patients with hematological malignancies positive for HHV 6 DNA during the infectious complication were enrolled in the study. Viral load in leukocytes and plasma of peripheral blood, antiviral M and G immunoglobulins and peripheral blood leukocytes count were evaluated. RESULTS: The majority of patients (66 out of 98, 67.3%) showed laboratory signs of latent HHV 6. Integrated HHV 6 was suspected in 2 patients due to high viral load (1.5x105 copies and 1.7x105 copies), but it was not confirmed subsequently. Additional testing of HCMV and EBV in patients with laboratory signs of active HHV 6 infection revealed the superiority of monoinfection over mixed infection (20 of 32, 62.5%). In cases of mixed infection, the most common co-infectant was HCMV observed in 9 out of 12 (75%) cases. Mild leukopenia accompanied HHV 6 active infection. CONCLUSION: Laboratory signs of latent HHV 6 tend to be prevalent in patients with hematological malignancies. In patients with laboratory markers of active HHV 6, the monoinfection demonstrated the superiority over mixed one. In cases of mixed infection, HCMV appeared to be the most commonly co-infectant. No cases of an integrated form of HHV 6 have been observed. The viral load of HHV 6 in leukocytes and blood plasma is almost 3 times lower in patients with a mixed infection than with a monoinfection. Active replication of HHV 6 was accompanied with mild leukopenia.

[Impact of current approaches to laboratory screening of donated blood and its components on hepatitis B virus infection in patients with blood system diseases]. / Vliianie sovremennykh podkhodov k laboratornomu obsledovaniiu donorov krovi i ee komponentov na infitsirovannost' virusom gepatita V u bol'nykh s zabolevaniiami sistemy krovi.

AIM: To evaluate the detection rate of markers for hepatitis B virus (HBV) in the blood samples taken from patients with blood system diseases, by applying the current approaches to examining donated blood and its components for markers of viral infections. MATERIAL AND METHODS: The investigation included blood samples from patients with blood system diseases (n=364) and donors (n=5,011). The results of laboratory screening of donated blood samples (n=13,081) were retrospectively analyzed. Commercial kits of reagents were used for immunochemical assay and polymerase chain reaction. RESULTS: Patients with blood system diseases were recorded to have markers of active HBV infection in 12.6% of cases, anti-HBc in 31.3%, and anti-HBs in 37.6%. A retrospective analysis of the results of screening donated blood samples showed the presence of markers for active HBV infection in 0.28% of cases. A prospective examination of blood donors revealed markers of HBV infection in 4.83% of cases, including those of active forms in 0.54% and anti-HBc in 4.79%. The markers of active HBV infection in donors were only anti-HBc IgM in 0.42% of cases. The blood samples from donors with an anti-HBs titer of >200 mIU/ml contained anti-HBc IgM in 10.5%. CONCLUSION: In the last 5-7 years, the detection rate of markers of HBV infection in the blood samples of patients with blood system diseases have remained at a high level. Screening for decreed markers fails to identify people with inapparent infections among the donors. Even high anti-HBs concentrations in the donated blood may be a risk for HBV transmission by transfusion to a recipient.

[The screening of donor blood on antibodies to nuclear antigen of hepatitis B virus as a tool of increasing of safety of transfusion for patients with diseases of blood system.]

Despite application of decreed modes of laboratory analysis of components of donors' blood, the risk of infection of recipients with hepatitis B virus continues to be actual. The isolated identification of HBsAg provides no control of all categories of persons infected with hepatitis B virus. The analysis of presence of antibodies to nuclear antigen of hepatitis B virus that are the first out of antiviral ones and are preserved for life, is an expedient technique of screening testing of donor's blood that permits implementing an additional selection of donors. During March 2014 - March 2015, cohort of regular anti-hepatitis B virus negative donors of blood and its components. The testing of blood samples for anti-hepatitis B virus can be recommended as a routine test increasing viral safety of blood transfusions for patients with diseases of blood system.

Hepatitis B and C viruses interference in coinfected multitransfused recipients.

Data on hepatitis B (HBV) and c (HCV) viruses interference in hematological patients are described. Patients with a hematological malignancy are at high risk of HBV and HCV infection as recipients of multiple transfusions. Results of the laboratory testing of 339 blood samples of patients treated at the National Research center for Hematology, Russian Federation, were studied. Among these patients, HBV/HCV coinfection markers were observed in 153 patients; HBV markers only, in 76 patients; HCV markers only, in 110 patients. The vast majority of coinfected patients had HBV DNA in blood (significantly more in HBsAg-negative patients: 100% vs. 82.8%, p = 0. 0005). HBsAg-negative coinfected patients had low HBV DNA levels (102-103ME/ml) and reduced (or completely absent) HCV RNA levels. The virus interference leads to a decrease in the viral nucleic acid concentrations. Thus, virus detection should include implementation of high sensitive molecular techniques (such as real-time PCR), and an enhanced set of serological HBV markers along with routine screening methods (HBsAg, anti-HCV).

[The alternative view on diagnostic of hyperlipoproteinemia, cholesterol lipoproteins of low density and effect of statins: a lecture].

The effect of statins occur in several stages: 1) inhibition in hepatocytes of synthesis of functionally specific pool of spirit cholesterol, polar mono-layer of lipoproteins of very low density; 2) activation of hydrolysis of triglycerides in lipoproteins of very low density, formation of apoE/B-100-ligand and absorption of lipoproteins of very low density by insulin-depended cells; 3) decreasing of content of and spirit cholesterol-lipoproteins of very low density in blood plasma; 4) activation of hydrolysis of triglycerides in lipoproteins of low density, formation of apoB-100-ligand and absorption of lipoproteins of low density by insulin-independent cells; 5) decreasing of level of and increasing of content of lipoproteins of high density. During first weeks of effect of statins occurs decreasing of concentration of triglycerides and unesterified spirit cholesterol-lipoproteins of very low density in blood plasma. Then, slower and more durational decreasing of level of spirit cholesterol-lipoproteins of low density occurs. The value of spirit cholesterol-lipoproteins of low density is primarily determined by content of palmitic saturated fatty acid in food, its endogenous synthesis from glucose and concentration of palmitic triglycerides and lipoproteins of very low density of the same name in blood plasma. The effect of preparations is biologically valid and corresponds to alternative hypolipidemic preparations. All these preparations have an effect following a common algorithm: they activate, using different mechanisms, receptor absorption of lipoproteins of very low density or lipoproteins of low density by cells. The level of spirit cholesterol-lipoproteins of low density in full measure depends on content of triglycerides in blood. The concentration of spirit cholesterol in blood plasma has a reliable diagnostic significance only under physiological content of triglycerides. The main criterion of diagnostic and control of hypolipidemic therapy biologically is content of triglycerides. The comprehension of differences in effect of hypolipidemic preparations within framework of common algorithm permits rationally combine them under treatment of both primary inheritable phenotypes of glucolipoproteins and secondary symptomatic types of glucolipoproteins under obligatory observation of strict dietary treatment.

[The PCR markers of viral infections under chronic gastritis in children].

The extended monitoring (up to 1 year 11 months) of PCR markers was implemented concerning viral infections: cytomegalovirus, Epstein-Barr virus, simple herpes virus type I and II, hepatitis B virus, hepatitis C virus and bacterial infection of Helicobacter pylori in bioassays (blood, biopsy material of mucous coat of stomach and inferior third of esophagus) from children with different types of chronic gastritis. In biological samples from patients with gastritis type A and type A + B DNA of hepatitis B virus (87% and 71% of patients correspondingly) and DNA of Epstein-Barr virus (63% and 67% of patients) were detected with high rate. Under gastritis type B and C these markers were detected significantly rarely (20-36%). Among patients with gastritis type A, B and A + B, the positive results on DNA of cytomegalovirus consisted 13-17%. In patients with gastritis type C DNA of cytomegalovirus was not detected. In any of analyzed samples no DNA of simple herpes virus type I and II was detected. The control of DNA of H. pylori demonstrated its presence in biological materials of 67% and 84% of patients with gastritis type B and A +B. This type of DNA was absent in patients with gastritis type A and C. Under gastritis type A, B and A+B, DNA of Epstein-Barr virus and DNA of hepatitis B virus detected more often in biological materials of mucous coat of stomach (71%-100%) and out of them simultaneously in blood in 33%-60% of examined patients and only in blood up to 29%. DNA of Epstein-Barr virus was detected in leukocytes of peripheral blood and DNA of hepatitis B virus both in plasma and leukocytes of peripheral blood. Under gastritis type C DNA of Epstein-Barr virus was always detected in leukocytes of peripheral blood (in 20% out of these patients simultaneously in biological material) and DNA of hepatitis B virus just as much in blood (plasma and/or leukocytes of peripheral blood) and biological materials. The lower concentrations (less than 700 copies/ml) DNA of hepatitis B virus in most samples were detected in absence of markers of hepatitis B virus. In patients with autoimmune gastritis and in absence of bacterial infection H. pylori (group I) or against its background (group III) PCR-markers of hepatitis B virus and Epstein-Barr virus were detected quite often. The evidence of persistence (in superior sections of digestive organs) of Epstein-Barr virus nad hepatitis B virus is detection of DNA of these viruses under their extended monitoring (up to 1 year 11 months) in biological samples from patients with autoimmune forms of gastritis type A and type A+B.

[Comparative analysis of occupational risk evaluation results through various methodic approaches].

Comparative analysis covered three models of occupational risk evaluation: (1) Method to evaluate risks at workplace, elaborated in Finland and recommended by International Work Safety Agency for Eastern Europe and Central Asia countries; (2) Method elaborated in Research Institute for Occupational Medicine with RAMSc under the direction of N.F. Izmerov and E.I. Denisov; (3) Method evaluating individual occupational risk, with consideration of work conditions and worker's health state, also elaborated in Research Institute for Occupational Medicine with RAMSc and Klin Institute of Work conditions and safety, approved in 2011 as methodic recommendations. Findings are that in contemporary Russia a unified method evaluating occupational risk is more expedient; the first method satisfactorily describes actual ratio of occupational risk levels and could be useful as an additional method for its evaluation, especially for psycho-social factors; the second method does not allow to evaluate occupational risk acceptably if absent longstanding occupational morbidity, but is recommended for risk evaluation in evidence-based medicine; the third method is recommended at federal level to fulfil requirements of Labour Code in Russian Federation and obligatory social insurance purposes.

[Laboratory diagnosis of herpesvirus infections in patients with acute leukemias].

The paper presents the results of monitoring the markers of herpes simplex viruses types 1 and 2, cytomegalovirus, Epstein-Barr virus, and human herpesvirus type 6 in the blood and bone marrow of patients with acute leukemias during induction multidrug therapy. Whether it is expedient to diagnose herpesvirus markers in patients with acute leukemias in the period of remission induction is discussed.

[Determination of type-specific synthetic peptide antibodies to hepatitis delta virus ]. / Opredelenie tipospetsificheskikh antitel k virusu gepatita del'ta na osnove sinteticheskikh peptidov.

Nine peptides from immunodominant (53-68 and 65-80 aa) and hypervariable (201-213 aa) regions derived from delta antigen sequences corresponding to 3 HDV genotypes were synthesized. Type specificity of antibodies to the resultant peptides was evaluated by indirect enzyme immunoassay with sera from patients with hepatitis D and asymptomatic carriers of anti-delta antibodies. Analysis of the results showed that HDV circulating in the Central Volga region belongs to type I in the majority of cases. High heterogeneity and changeability of HDV genome during the period of transition from acute forms to asymptomatic carriership was revealed. Possibility of circulation of new hybrid HDV strains causing mixed infection in Russia is discussed.

[Bacterial polysaccharides of polymyxan 88A. Basic characteristics and extent of possible uses]. / Bakterial'noi polisakharid polimiksan 88A. Osnovnye kharakteristiki isfery vozmozhnogo primeneniia.

A new high-viscous polysaccharide polymyxan from Bacillus polymyxa 88A is described. Polymyxan consists of an acid high-viscous polysaccharide (Mw 1-10 MD) and a neutral low-viscous polysaccharide (Mw 100-300 kD), which is a glucomannan containing equal amounts of monosaccharides and traces of uronic acids. The acid high-viscous polysaccharide consists of 36% glucose, 36% mannose, 7% galactose and 21% glucuronic acid. Data are presented on the application of polymyxan in baking industry and for preparation of drilling muds.