[Comparative evaluation of the effectiveness of narlaprevir in the composition of interferon and interferon-free treatment regimens for patients with chronic hepatitis C].

AIM: Our aim was to give a comparative assessment of the effectiveness of using narlaprevir in combination with pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) and interferon-free mode in patients with chronic hepatitis C (CHC). MATERIALS AND METHODS: The prospective cohort study included 187 patients infected with genotype 1b of hepatitis C virus. Of these, 107 (the 1st group of patients) received narlaprevir 200 mg once a day, ritonavir 100 mg once a day, Peg-IFN-alpha-2a 180 mkg subcutaneously once a week and ribavirin at a dose depending on body weight (10001200 mg per day) for 12 weeks, and then the standart "dual" therapy (Peg-IFN-alpha-2a + ribavirin) was continued until 24 weeks. Patients of the 2nd group (n=80) received antiviral therapy in an interferon-free mode. They received narlaprevir 200 mg once daily, ritonavir 100 mg once daily, and daclatasvir 60 mg once daily for 12 weeks. RESULTS: With the use of an interferon-containing treatment regimen, a sustained virological response was achieved in 92.4% of previousle untreated patients with CH and in 66.7% patients with "unsuccessful" experience of the previous course of treatment. In 5.6% of cases, there was an early termination of treatment due to the development of adverse events. 80 (100%) patients completed the course of treatment with narlaprevir in the interferon-free mode. Sustained virological response was reached by 75 (90%) patients. CONCLUSION: Real clinical practice indicates that the use of narlaprevir in the non-interferon mode is not inferior in efficiency to the interferon-containing treatment regimen and demonstrates a more favorable safety profile.

[DETECTION OF DEGREE OF MICROECOLOGICAL DISTURBANCE OF INTESTINE BASED ON CALCULATION OF LOCAL ANTIOXIDANT INDEX].

AIM: Evaluation of dysbiotic condition of intestine based on determination of local antioxidant index (LAI). MATERIALS AND METHODS: 155 patients with bacteriologically confirmed intestine dysbacteriosis were examined: 20 individuals with normobiocenosis of the intestine served as control. Feces dilution 10⁻² was used for biochemical study. Catalase, superoxide-dismutase activity and level of malonic dialdehyde was evaluated photometrically by the value of optical density of the samples. Microbial landscape of feces was studied by a bacteriologic method with parallel determination in samples of coprofiltrates of activity of the indicated enzymes and content of malonic dialdehyde. Evaluation of disturbances of microecology of the intestine was carried out by a biochemical method by calculating local antioxidant index in juxtaposition with microbial map data. RESULTS: LAI parameter was significantly higher than 20 in coprofiltrates of people with intestine normobiocenosis. In patients with detected intestine dysbacteriosis, depending on its degree, LAI parameter, changes were registered in the range from negative to 20. Dysbacteriosis in a part of patients had a prolonged character, LAI was lower than 14, that reflected the presence of a persistent inflammation. A tendency of normalization of microbial ecology and growth of LAI was observed during administration of a probiotic preparation. CONCLUSION: A screening criteria is proposed, that differentiates the degree of severity of intestine dysbacteriosis based on calculation of local antioxidant index.

[The time-of-flight mass spectrometer intra-specific diagnostic of strains of Escherichia isolated from patient].

The time-of-flight mass spectrometer analysis of freshly separated human colibacillus populations for identification of markers of proteom specific for hemolytic and non-hemolytic strains, Escherichia-associant of opportunistic enterobacteria. The material consisted of 20 strains of mono-population of hemolytic Escherichia; 100 strains of mono-population of non-hemolytic Escherichia; 15 non-hemolytic strains isolated from association with opportunistic enterobacteria. The protein profiling was implemented on mass spectrometer MALDI-TOF MS Autoflex "Bruker Daltonik". The value within type of peak mass-charge with 100% intensity equal to 9000 Da can be used as a differentiating indication of detection of hemolytic Escherichia at mass-spectrometer biotyping. The proteom characteristics of strains of various populations within Escherichia coli species are given. The taxon-specific markers for proteom differentiation of population of Escherichia are given too.

[PROTEOMIC MASS-SPECTROMETRIC ANALYSIS OF FRESHLY ISOLATED ESCHERICHIA COLI STRAINS].

AIM: Time-of-flight mass-spectrometric analysis of colon bacilli populations freshly isolated from humans for identification of proteome markers, that are characteristic for hemolytic and non-hemolytic strains, E.coli--associants of opportunistic bacteria. MATERIALS AND METHODS: 20 strains of monopopulation of hemolytic E.coli; 100 strains of monopopulation of non-hemolytic E. coli; 15 non-hemolytic strain, isolated from association with opportunistic bacteria. Protein profiling on MALDI-TOF MS Autoflex "Bruker Daltonik" mass-spectrometer. RESULTS: Value within species for mass-charge peak with 100% intensity of 9000 Da could be a differential sign for isolation of hemolytic E.coli during mass-spectrometric biotyping. CONCLUSION: Proteomic characteristics of strains from various populations within E.coli are given. Taxon-specific markers for proteomic differentiation of E.coli populations are established.

[Indexes of immunity and local protection in humans with intestine dysbacteriosis].

AIM: Study indexes of immunity and local protection in humans with intestine dysbacteriosis. MATERIALS AND METHODS: Qualitative and quantitative intestine microbiocenosis, content of gamma-interferon (EIA method) in coprofiltrates in 204 individuals were studied, data from immunograms of 123 individuals with bacteriologically confirmed dysbacteriosis were analyzed. RESULTS: The presence of immune deficiency mainly by T-cell type was established in 92.7+/-2.4% of individuals with intestine dysbacteriosis. Significant variations in -interferon content in coprofiltrates of examined individuals was detected (from no less than 5 pcg/ml to 240 pcg/ml), a statistically significant dependence of gamma-interferon content in coprofiltrates on the number of opportunistic microbes and atypical escherichia (including hemolytic) in intestine microbiocenosis was determined. CONCLUSION: The presence of T-cell type immune deficiency in individuals with intestine dysbacteriosis combined with a reduced local protection, and the content of gamma-interferon in coprofiltrates gives evidence not only on the reduction of local protection but also to some extent mirrors the degree of this reduction.

[Indexes of local cytokine status in individuals with intestine dysbacteriosis].

AIM: Determination of the content of various cytokines in coprofiltrates of individuals with bacteriologically confirmed intestine dysbacteriosis. MATERIALS AND METHODS: Qualitative and quantitative content of large intestine microbiocenosis was studied; IFNγ, pro-inflammatory (IL-2, IL-6, IL-8, IL-1ß) and anti-inflammatory (IL-4, IL-10) content was determined using EIA in coprofiltrates of 139 individuals aged 18 - 60 years. All the indexes were juxtaposed with the cytokine index (CI): RESULTS. A high content of IL-2, IL-4 and IL-10 with normal levels of IL-1ß, IL-6 and IL-8 was established. A comparable content of bifidobacteria, lactobacilli and escherichia was detected in individuals with various CI index; in individuals with CI above 1 c.u. and above 10 c.u., against the background of proportionally intensifying IFNγ induction, an increase of quantity of escherichia with decreased enzymatic activity and frequent detection of opportunistic enterobacteria, staphylococci and Candida genus fungi is noted. CONCLUSION: The presence of opportunistic microflora at low content of IFNγ with CI of less than 1 c.u. could be evaluated as a dysbiotic reaction, and the presence of opportunistic microflora against the background of high IFNγ content with CI of above 10 c.u.--as a development of systemic inflammation due to translocation of dysbiotic microflora into the bloodflow.

[Biochemical criteria for severity of colonic dysbacteriosis].

The purpose of the investigation was to estimate the content of malondialdehyde (MDA) in the coprofiltrates of human beings with bacteriologically verified colonic dysbacteriosis and to clarify a relationship of the amount of MDA in the coprofiltrates to the degree of the abnormal qualitative and quantitative composition of microbiocenosis. Specimens from 109 subjects aged 19 to 56 years were examined. The change in the level of MDA in the coprofiltrates was found to correspond to the impairment in the composition of microbiocenosis. The comparison of the coprofiltrate content of MDA with enteric microbiocenotic changes allows one to consider that MDA levels may serve as a biochemical criterion for the degree of dysbacteriosis and be used as an additional method for its diagnosis.

[Features of microbiocenosis composition of large intestine of humans with various degree of local metabolic disorders].

AIM: Detection of features of qualitative and quantitative composition of large intestine microbiocenosis of humans with various degree of local metabolic disorders during dysbacterioses due to various causes. MATERIALS AND METHODS: Microflora of large intestine and content of malonic dialdehyde (MDA) in coprofiltrates of 330 adult humans with large intestine dysbacterioses due to various causes were studied. RESULTS: It was established, that high MDA content in coprofiltrates matches higher quantities of opportunistic microorganisms and atypical escherichia in microflora composition of large intestine. Relation of MDA composition in coprofiltrates and factors that cause dysbacteriosis were not detected. CONCLUSION: The studies performed give evidence that changes in local metabolic activity may be a single mechanism of development of large intestine dysbacterioses that are caused by various factors.

[Measures of local non-specific resistance during of colon dysbiosis].

AIM: To study several parameters of local non-specific resistance during development of experimental dysbiosis caused by administration of wide spectrum antibiotic. MATERIALS AND METHODS: Objects of the study were colonocytes and coprofiltrates from 120 outbred mice developing experimental dysbiosis, in which activity of antioxidant enzymes (superoxid dismutase [SOD] and catalase) and level of one of the final product of lipid peroxidation--malondialdehyde (MDA). RESULTS: Decrease of SOD and catalase activity and significant increase of MDA level during development of experimental dysbiosis were established, which were associated with decreased activity of oxygen-dependent bactericidal systems of colonocytes and changes in composition of colon microbiocenosis. CONCLUSION: It was suggested that changes in parameters of local non-specific resistance could be one of mechanisms, which cause alteration of microbiocenosis composition during colon dysbiosis.

[Microbiocenosis of large intestine in persons with dysfunctional disorders of biliary tract].

AIM: To study prevalence of hemolytic Escherichia in microbiocenosis of large intestine in 501 adult persons from Rostov-on-Don city. MATERIALS AND METHODS: Comparison of qualitative and quantitative composition of large intestine microbiocenosis in 248 persons with ultrasound examination of functional state of biliary tract was performed. RESULTS: Statistically significant dependence of the rate of hemolytic Escherichia detection in microflora of large intestine from presence of dysfunctional disorders of biliary tract (biliary tract dysfunction) was revealed. Difference in character of microecological changes in large intestine of patients with such disorders and persons treated with wide-spectrum antibiotics was established. It was revealed that main feature of large intestine dysbiosis in patients with biliary tract dysfunction was the presence of significant quantity of hemolytic Escherichia as part of this compartment's microflora. CONCLUSION: Hypothesis about possible role of functional disorders of biliary tract as a primary cause of microecologic imbalance was proposed.