[The long-term prospective study of patients with liver cirrhosis after elimination of the hepatitis C virus].

AIM: To study liver function and portal hypertension, incidence and risk factors of liver-related complications, including hepatocellular carcinoma (HCC), in patients with HCV-related liver cirrhosis achieved sustained virologic response (SVR) after direct-acting antiviral therapy. MATERIALS AND METHODS: Patients with HCV-related liver cirrhosis were followed up after achievement SVR with assessment of liver function parameters, portal hypertension, Model for End-stage Liver Disease (MELD) and Сhild Pugh (CP) scores, complications development, including HCC, every 36 months. The median follow-up duration was 24 [18; 30] months after end of treatment. RESULTS: At last observation, a number of cirrhotic patients with CP class A increased from 72% to 85%, with CP class B reduced from 23.5% to 12.5%, with CP class C from 4.5% to 2.5%. In 89% patients were identified a regress of liver fibrosis (from 23.5 [16.9; 28] to 15.0 [10.2; 21.3] kPa,p0.005), each third patient reduction of fibrosis stage to F2/F3. In 19 (9.5%) patients were occurred liver-related complications, including HCC (in 9 patients). Baseline high total bilirubin level (34 mol/l) (Hazard ratio (HR) 11.5, 95% confidence interval (CI) 2.357.8,р0.005) and ascites (HR=17.6, 95% CI 2.1144.8,p=0.008) were independent risk factors associated with HCC development. CONCLUSION: The risk of HCC development remains in patients with HCV-related liver cirrhosis, despite on eradication of hepatitis C virus. Therefore, these patients should continue to undergo more intensive examination (ultrasound examination and determination of alfa-fetoprotein level each 36 months), including contrast-enhanced methods of imaging, the frequency of which should be determined.

[Topical problems of empiric therapy of community-acquired pneumonia in outpatient practice].

Community-acquired pneumonia is one of prevalent infectious respiratory diseases. Adequate treatment of community-acquired pneumonia, with consideration of the disease severity and microbial resistence, remains extremely topical. The article covers contemporary views of community-acquired pneumonia treatment standards. The authors described results of personal research aimed to study antibacterial treatment for community-acquired pneumonia on outpatient basis over 2004-2012, evaluated correspondence of the treatment to the national clinical recommendations.

[Impact of interleukin-10 and interleukin-28 gene polymorphisms on the development and course of lupus nephritis].

AIM: To assess the relationship of the carriage of IL-10-1080 G/A and IL-28 rs8099917 C/T polymorphisms to the course of lupus nephritis (LN). SUBJECTS AND METHODS: Ninety-nine patients with systemic lupus erythematosus (SLE), including 68 with LN, were examined. Gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of the clinical manifestations of LN was analyzed; renal survival (RS) was estimated by the Kaplan-Meier method. RESULTS: Ten-year RS rates were 80 and 86% of the patients with and without the mutant IL-10 allele, respectively (p = 0.78). The 10-year RS was lower (75%) in carriers of the mutant IL-28 rsl2979860 allele than in patients without this mutant allele (83%; p = 0.049) and in those of the mutant IL28 rs8099917 allele than in patients without the above mutant allele (67 and 88%, respectively; p = 0.047). LN patients, carriers of the mutant IL-10-1028 G/A allele, were observed to have higher-grade proteinuria in the presence of nephritic syndrome (mean 6.1 g/l) than those without the mutant allele of this gene (mean 2.9 g/l; p = 0.034). However, the mutant allele carriers responded to treatment better (p = 0.050). The mutant IL-10 and IL-28 alleles were unassociated with the development of rapidly progressive nephritis, the activity of a renal lupus process, and the rate of onset of SLE and LN. CONCLUSION: In the LN patients, the carriage of the mutant IL-10 allele A is associated with a better response to treatment and that of the mutant IL-28 allele is linked to the severe course of the disease.

[Alterations of the complement system in patients with catastrophic antiphospholipid syndrome].

AIM: To investigate alterations of the complement system in patients with catastrophic antiphospholipid syndrome (CAPS). SUBJECTS AND METHODS: Four patients (2 men aged 23 and 40 years and 2 women aged 39 and 58 years) diagnosed as having CAPS, including 3 patients with systemic lupus erythematosus and secondary antiphospholipid syndrome (APS) and 1 patient with primary APS, were examined. The activity of the complement components C1-C5 and total hemolytic activity were determined in all the patients at the moment of an acute episode and in 1 patient after treatment. RESULTS: The activity of the studied complement components and total hemolytic complement activity proved to be significantly decreased in all the patients. That of complement components recovered after treatment using fresh frozen plasma. The possibility and mechanisms of complement system activation in the patients with CAPS are discussed. CONCLUSION: The preliminary results obtained by the examination of few cases may lead to the conclusion that the complement system may be involved in the development of CAPS.

[Prognostic value of allelic variants affecting the hemostatic system in the development of antiphospholipid syndrome and kidney lesion in patients with systemic lupus erythematosus].

AIM: To analyze the prognostic value of the polymorphisms of the thrombophilic genes: plasminogen activator inhibitor type 1 (PAI-1) (-675 4G/5G), factor XIII (FXIII) (G485T), fibrinogen (FBG) (G(-455)A), glycoprotein Ia (GPIa) (C807T), glycoprotein IIIa (GPIIIa) (T106C), and p22phox (C242T), as well as protein genes involved in the pathogenesis of endothelial dysfunction: subunits of p22phox NADH-oxidase (p22phox) (C242T), endothelial NO-synthase (eNOS) (G894T), and methylenetetrahydrofolate reductase (MTHFR) (C677T) for the development of antiphospholipid syndrome (APS) and a type of progressive lupous nephritis (LN) in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: One hundred patients with SLE were examined and, according to the presence of clinical and laboratory signs of APS were divided into 2 groups: 1) 50 SLE patients with APS; 2) 50 SLE patients without APS who were matched for gender and age with Group 1 patients. The gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of clinical manifestations of APS and the type of progressive nephritis were analyzed in view of the genotypes of the patients. RESULTS: Comparison of SLE patients with and without SLE revealed no statistically significant differences in the rates of alleles and genotypes. The patients with arterial and/or venous thrombosis in the presence of APS more frequently displayed a minor allele (T) and genotype (TT) of the p22phox gene than those with APS without thrombosis: T, 64.5 and 34%, respectively (p = 0.033); TT, 36 and 7% (p = 0.021); odds ratio (OR), 2.1 at 95% confidence interval (CI), 1.5 to 22.7). In the APS patients with livedo reticularis, the minor allele (T) and genotype (TT) of the eNOS gene were more common than in those without livedo: T, 33 and 10%, respectively (p = 0.019); TT, 15 and 0% (p = 0.031); OR, 2.49 at 95% CI, 1.2 to 28.9). In the patients with AFS and rapidly progressive LN (RPLN), the minor allele (T) and genotype (TT) of the MTHFR gene were much more frequently encountered: T, 46 and 27%, respectively (p = 0.038); TT, 30 and 0% (p = 0.033); OR, 3.1 at 95% CI, 1.4 to 32.7). The group of patients without APS exhibited no relationship between the examined polymorphisms and kidney lesion. CONCLUSION: The mutant allele of the p22phox gene increases the risk of arterial and venous thrombosis; the polymorphism of the eNOS gene may be related to the higher incidence of impaired blood microcirculation in SLE concurrent with APS. The risk of RPLN in SLE patients with APS is probably associated with MTHFR gene mutation.

[Severe adverse events from treatment with genetically engineered biological agents in patients with rheumatic diseases].

AIM: To assess the risk of severe adverse events (AEs) within 6 months after treatment with biological agents in patients with rheumatic diseases (RD). SUBJECTS AND METHODS: The 6-month open-label trial included 107 patients with rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, and other RDs who received genetically engineered biological agents (GEBAs), primarily rituximab (n = 66) and infliximab (n = 31). RESULTS: The majority of patients were noted to have improvements, including complete and partial remission in 62 (57.9%) and 42 (39.3%), respectively. There were mild or moderate AEs in 22 (20.6%) of the 107 patients, severe AEs in 6 (5.6%): grade IV neutropenia in 2 patients (after the use of rituximab), severe infusion reactions in 2 (after the administration of infliximab and rituximab), and systemic infections in 2 (fatal nocardial sepsis after rituximab treatment and unspecified sepsis after infliximab treatment). CONCLUSION: The rate of serious AEs, mainly infusion AEs and infections during treatment with infliximab, rituximab, and other GEBAs proved to be relatively low in patients with different RDs. At the same time, the use of biological agents could lower RD activity in the presence of severe visceral injuries refractory to conventional immunosuppressive therapy.

[The integral evaluation of oxidative anti-oxidative status in patients of neuroreanimation department].

The article presents comparative evaluation of serum total oxidizing and total anti-oxidizing activity in reanimation patients with severe cranio-cerebral injury and ischemic and hemorrhagic strokes. Due to irregularity of experimental groups in a number of demographic and clinical indicators the new estimated indicator was proposed. The normalized coefficient of oxidation made it possible to apply comparative evaluation of expression of oxidative anti-oxidative imbalance in these groups. The characteristics are presented concerning the oxidative derangements in the studied groups during acute period of disease.

[The study of quality of life of epileptic children with the special questionnaire QOLCE].

The objective was to create a Russian version of the special quality of life (QOL) questionnaire QOLCE for children with epilepsy and to use it to study QOL. The language and cultural adaptation of the questionnaire has been carried out. The final pilot version was administered to 50 mothers of children with epilepsy. The age of patients was from 4 to 16 years (mean 8.94 +/- 4.21), mean age at-disease-onset was 5.30 +/- 3.33 years (from 1 month to 12 years), mean duration of epilepsy was 4.36 +/- 3.48 years, mean duration of treatment was 3.28 +/- 2.58 years. Idiopathic epilepsy was diagnosed in 17 (34%) children, symptomatic - in 13 (26%), cryptogenic - in 20 (40%). The QOLCE was acceptable for all parents. For the majority of items, the mean percentage of missing answers was 3.09%; for Social activity and Stigma subscales the values were 15%. The lowest scores were shown on subscales Physical Restrictions (49.16 +/- 20.31), Cognitive Function (55.78 +/- 23.36), General Health (59.90 +/- 26.16). The highest scores were on the subscale Social Activity (78.08 +/- 26.88). The authors believe that the further testing of the Russian version of the QOLCE is needed.

[Severe Wegener's granulomatosis successfully treated with rituximab].

The paper discusses the problems of the diagnosis and treatment of Wegener's granulomatosis, the most common anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. It describes a clinical case in which the administration of rituximab could achieve remission of severe Wegener's granulomatosis in a young man having numerous adverse reactions associated with the long-term use of high- and average-dose glucocorticoids and nonselective immunosuppressive agents. A place of rituximab in current drug therapy for Wegener's granulomatosis is shown.

[Evaluation of the function of the hematoencephalic barrier in victims with craniocerebral trauma in critical state]. / Otsenka funktsii gematoéntsefalicheskogo bar'era pri kriticheskikh sostoianiiakh u postradavshikh s cherepno-mozgovoi travmoi.

Estimates of the relative-entry coefficient, molecular profile of the cerebrospinal fluid and of the molecular blood profile based on the comparison of concentrations of proteins with different physical-and-chemical properties enable an evaluation of the function of the hematoencephalic barrier in victims with craniocerebral trauma in critical state. It was possible to state, with such approach in use, that the regulatory and protective functions of the hematoencephalic barrier were changing differently in favorable and unfavorable trauma outcomes, which must be duly considered in choosing a treatment tactics for the above category of victims.

[Antioxidants in malignant neoplasms in humans and animals]. / Antioksidanty v zlokachestvennykh opukholiakh cheloveka i zhivotnogo.

This review is devoted to the role of low molecular weight antioxidants and antioxidant enzymes in cancerogenesis. The data on accumulation of lipid-soluble and water-soluble antioxidants in a number of malignant human and experimental tumors especially in the renal cell carcinoma tissues are analyzed. A possibility is discussed concerning the pro- and anticarcinogenic effects of the abundant tumor content of antioxidants. Implication of antioxidants in tumor resistance to chemotherapeutic drugs and ionizing radiation is discussed.

[Permeability of the blood-brain barrier in severe craniocerebral trauma]. / O pronitsaemosti gematoéntsefalicheskogo bar'era pri tiazheloi cherepno-mozgovoi travme.

Permeability of the blood-brain barrier was studied by comparing the molar concentrations of albumin and alpha 2-macroglobulin in the spinal fluid and blood of patients with severe brain injury. If the outcome was good, the selective permeability of the barrier was shown to be fully retained, which meant that its regulatory and protective functions remained normal. If the outcome was poor, the selective permeability changed to a greater extent and the alterations found suggested that the regulatory function of the barrier was preserved with simultaneous loss of its protective properties. More marked changes in the function of blood-brain barrier and in the protein composition of spinal fluid occurred with simultaneously elevated intracranial pressure.

Lipid peroxidation in malignant tumors of human kidneys.

The intensity of ascorbate-dependent free radical oxidation of endogenous lipids in malignant tumor tissue of human kidneys was studied. The LPO induction period was markedly increased in renal-cell carcinoma and malignant mesenchymal tumors compared to normal renal cortex. The content of alpha-tocopherol in cancer tissue lipids was considerably (7-fold) increased compared to that in normal renal cortex, which explains high antioxidant activity of these carcinomas. A less pronounced increase in the content of alpha -tocopherol in lipids of malignant mesenchymal tumors compared to the cortex (2-fold) can also contribute to their LPO resistance.

[Accidental involution of the thymus after splenectomy (an experimental study)]. / Aktsidental'naia involiutsiia timusa posle splenéktomii (immunogistologicheskoe issledovanie).

Using immunological, general clinical and luminescent histochemical methods experimental study of immunological status and bioamine-containing thymus structures was performed on third, seventh and fifteenth postsplenectomy days in 90 outbred albino male rats. Splenectomy leads to significant changes in blood immunological parameters and morphofunctional state of thymus bioamine-containing structures. Significant increase of biogenic amines content in all thymus structures, leukocyte number, complement activity neutrophilic granulocytes phagocytic activity, were registered in 3 days. Further growth of bioamine content, decrease of cortical and medullary substances diameter, significant number growth of juvenile forms of mast cells were observed in 7 days. Essential decline in erythrocyte number, hemoglobin and IgG and IgA content, leukocytosis with leukemoid reaction development were defined in blood formula. On 15th postsplenectomy day maximal biogenic amine concentration, especially histamine was reached and further reduction in cortex and medulla as well as decline of all the immunoglobulins and decrease of neutrophilic granulocytes phagocytosis were determined. Thus, splenectomy and subsequent development of accidental involution leads to secondary immunodeficiency and severe anemia.

[The possible role of alpha 2-macroglobulin in regulating the immune components of the brain in tick-borne encephalitis]. / Vozmozhnaia rol' al'fa 2-makroglobulina v reguliatsii immunnykh komponentov mozga pri kleshchevom éntsefalite.

In tick-borne encephalitis certain immunopathological reactions develop in the tissues of the central nervous system; alpha 2-macroglobulin may serve as the marker of the activity of these reactions. The dynamic study of liquor taken from 16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE), 8 patients with severe craniocerebral traumas accompanied by meningitis and 10 patients with osteochondrosis was made. As revealed in this study, in TBE patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable during the acute period of the disease.

[The permeability of the hemato-encephalic barrier and the proteolytic potential of the cerebrospinal fluid in severe craniocerebral trauma]. / O pronitsaemosti gematoéntsefalicheskogo bar'era i proteoliticheskom potentsiale likvora pri tiazheloi cherepno-mozgovoi travme.

To study blood-brain barrier permeability and proteolytic changes in in patients with severe brain injury and to evaluate their impact on its course and outcome, the concentrations of albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin were examined in 58 victims by enzyme immunoassay. The control group comprised 20 patients examined for lumbar discal hernia. The studies indicate that early severe brain injury showed blood-brain barrier dysfunction whose severity can be detected by the spinal fluid levels of albumin, plasminogen, and alpha 2-macroglobulin. Proteolytic changes in spinal fluid are determined by its albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin concentrations and affect the development of secondary brain lesion and they are of practical value.

[The content of the protein markers of hemato-encephalic barrier permeability in the cerebrospinal fluid in severe craniocerebral trauma]. / Soderzhanie belkov--markerov pronitsaemosti gematoéntsefalicheskogo bar'era v spinnomozgovoi zhidkosti pri tiazheloi cherepno-mozgovoi travme.

The CSF levels of albumin, alpha 2-microglobulin and IgG were studied in patients with severe brain injury. Elevated CSF levels of albumin and alpha 2-microglobulin were found in more severe patients. The level of IgG level was within the normal range. Endogenic protease-bound alpha 2-microglobulin may cause secondary cerebral tissue lesion, by closing the vicious circle.

[Accumulation of vitamin E in dimethylnitrosamine-induced kidney tumors in rats with various levels of alpha-tocopherol supplementation]. / Nakoplenie vitamina E v opukholiakh pochek krys, indutsirovannykh dimetilnitrozoaminom, pri razlichnom obespechenii zhivotnykh alpha-tokoferolom.

The effect of a long-lasting loading with alpha-tocopherol on the development of dimethylnitrosamine-induced kidney tumors was investigated in 55 non-bred white male rats. The carcinogen was repeatedly introduced into the stomach by means of a gastric tube. Starting 24 days after the last administration of the carcinogen the alpha-tocopherol loading began and lasted up to the end of the experiment. 21 rats were loaded with vitamin E introduced into the stomach, 5 times a week at a dose of 70 mg/kg body weight. 17 rats received sunflower seed oil--the vitamin E solvent; other 17 rats received only standard ration. The control group (20 rats) were not treated with the carcinogen. One part of these rats received alpha-tocopherol by the above schedule while another part--sunflower oil alone. It was shown that the alpha-tocopherol loading had no effect on the incidence of renal tumors. Nevertheless it enhanced to some extent the rate of their development as well as the incidence of blastomes in other organs. Based on histological examination, tumors developed in kidneys were of epithelial and mesenchymal origins with the mesenchymal tumors occurring more frequently (63-69% of the total). Vitamin E content in tumor tissue of rats, loaded or not loaded with alpha-tocopherol, was much higher than that in intact kidneys of corresponding control animals, suggesting a high tumor tropism of this vitamin. Total lipid concentration of tumor tissue was 1.5 times lower than that of intact kidneys. Histological nature of tumors had no visible effect on their vitamin E and total lipid content.

[Marker proteins in cerebrospinal fluid of patients with grave craniocerebral injury]. / Soderzhanie belkov-markerov v spinnomozgovoi zhidkosti pri tiazheloi cherepno-mozgovoi travme.

The permeability of the blood-brain barrier for the cerebrospinal fluid marker proteins has been assessed in patients with grave craniocerebral injuries. The content of albumin and alpha 2-macroglobulin in the survivors decreased with time and by day 7 after the injury was virtually normal. In patients who died the content of these proteins was reliably increased starting from day 1. By day 7 the content of albumin in the cerebrospinal fluid approached the norm in this group, whereas the content of alpha 2-macroglobulin remained increased. The level of IgG surpassed the normal value on day 1 only in the patients who died, and later it did not differ from the norm in both groups.