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We analyzed the expression of molecular targets of natriuretic action of prolactin in different layers of the kidney in the rat model of cholestasis of pregnancy. Sodium bicarbonate cotransporter NBCe1 was most sensitive to the conditions of cholestasis and cholestasis of pregnancy: the expression NBCe1 mRNA and protein in the renal outer medulla decreased in comparison with the normal. All forms of cholestasis affected the mRNA expression of sodium-potassium chloride co-transporter NCC, α-subunit of the ENaCα epithelial sodium channel, and Nedd4-2 ubiquitin ligase in different layers of the kidney. The obtained data suggest that prolactin provides fine tuning of various sodium transporters in different parts of the nephron under pathological conditions.

Progesterone (P4) and its analogues regulate various reproductive processes, such as ovulation, implantation, pregnancy maintenance and delivery. In these processes, an important role is played by the immune cells recruited to the female reproductive organs and tissues, where they are exposed to the action of P4. Progestins regulate cellular processes, acting through nuclear steroid receptors (nSRs), membrane P4 receptors (mPRs), and through the sensors. It remains unclear, what type of receptors is used by P4 and its derivatives to exert their effect on the immune cells and how similar their effects are in different types of these cells. We have previously synthesized new progesterone derivatives, among which two selective mPRs ligands, not interacting with nSRs were identified. The objective of this study was to examine the effects of P4 and new selective mPRs ligands on the expression of pro- and anti-inflammatory cytokines in activated human peripheral blood mononuclear cells (PBMCs), THP-1 monocyte cells, and Jurkat T cells. It was demonstrated that the action of P4 and selective ligands was unidirectional, but in different types of the immune cells, their effects were different, and sometimes even opposite. In PBMCs, exposure to these steroids resulted in the increase of mRNA and secreted protein levels of IL-1β, TNFα, and IL-6 cytokines, as well as in the increase of INFγ mRNA level, decrease of IL-2 mRNA level, increase of TGFβ mRNA level, and decrease of IL-4 mRNA and IL-10 secreted protein levels. In monocytes, similarly to PBMCs, expression of IL-1β and TNFα mRNA was increased, but expression of IL-10 was also increased, and the TGFβ expression statistically significantly remained the same. In Jurkat T cells, expression of IL-2 and TNFα mRNA decreased, while expression of IL-10 increased, and expression of TGFβ did not change. Thus, progestins act on the immune cells through mPRs and have both pro- and anti-inflammatory effects, depending on the phenotypes of these cells. The data obtained are important for understanding the complexity of the immune system regulation by progestins, which depends on the type of the immune cells and individual characteristics of the immune system.

We studied possible involvement of prolactin in the regulation of bicarbonate biodynamics using female rat model of cholestasis of pregnancy induced by transplantation of the donor pituitary under the renal capsule of a recipient (hyperprolactinemia) and bile duct ligation (cholestasis). The concentration of bicarbonates in the bile and blood, their excretion, clearance, and reabsorption, as well as glomerular filtration rate and excretion of sodium ions were assessed. It was found that the main effect of prolactin was directed to the kidney-regulated pool of bicarbonates and consisted in stimulation of their clearance and inhibition of reabsorption, which led to a decrease in bicarbonate blood concentration. Parallel influence of prolactin on the clearance of bicarbonates and sodium ions was observed.

Cholestasis of pregnancy is a pathology associated with disruptions in the bile flow and dysregulation of salt and water homeostasis. Prolactin is one of the most important regulators of salt and water balance. Changes in the expression of long and short isoforms of the prolactin receptor (PrlR) and mediators of prolactin signaling were studied by immunoblotting and RT-qPCR in the rat kidney cortex and outer medulla in the model of cholestasis of pregnancy. Both PrlR isoforms were shown to participate in the effects of prolactin in cholestasis of pregnancy. Direct impact of prolactin on the kidney has been demonstrated: (i) mRNA expression of both PrlR isoforms in the kidney depended on the physiological conditions and prolactin levels; (ii) expression of pSTAT5, a key mediator of the long PrlR isoform signaling, was increased in animals with cholestasis of pregnancy; (iii) in the case of long PrlR isoform predomination, expression of mRNAs for the prolactin signaling inhibitors SOCS3 and PIAS3 was upregulated (the genes of these regulators contain STAT-responsive elements in their promoters); (iv) expression of the mRNA for galactose-1-phosphate uridyltransferase (GALT), a molecular target of the PrlR short isoform, was decreased in the kidney outer medulla.

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

Background : Infectious complications — the leading cause of mortality in patients with multiple myeloma (MM), their appearance is regarded as an adverse prognostic factor in the course of the disease. Objective : The aim of our study was to evaluate the clinical and immunological features of infectious complications in patients with G- immunochemical MM to find the most informative indicators in their forecasting. Methods : A randomized controlled trial was made. All patients were divided into 3 groups for comparison: Group 1 (n =47) — MM patients, G-immunochemical variant with infection, Group 2 (n =54) — MM patients, G-immunochemical option no infectious complications, and Group 3 (n =125) — healthy volunteers. Research material was deoxygenated blood taken on admission of a patient to the hematology department before the pathogenetic treatment. Identification of G-variant was carried by immunofixation and electrophoresis. The immune status was assessed by indirect immunofluorescence. The concentration of IgA, M, E and G, and the levels of IL 2, IL 4, IL 8, TNF α, IFN γ in serum was determined by enzyme immunoassay. The activity of neutrophil granulocytes (NG) was studied by chemiluminescent analysis of spontaneous and induced production of reactive oxygen species. Statistical analysis was performed using the software STATISTICA v. 8.0 (USA). Results : We analyzed data from 101 patients with MM and 125 healthy volunteers. The average age of MM patients was 60.53±6.78 years. The group of healthy volunteers was similar in sex and age to groups of patients with MM. In patients with MM in the presence of infectious complications the researchers detected combined secondary development of T and B cell immunodeficiency, changes in non-specific immunity depended on the stage of the disease, unidirectional irregularities in spontaneous and induced chemiluminescence activity NG in II stage disease and multidirectional irregularities in stage III (p =0.045). Prevalence of the content of proinflammatory cytokines on inflammatory (p

Using immunohistochemical method with semiquantitative analysis of images, we showed that mrp2 expression in response to cholestasis decreased in hepatocytes and cholangiocytes, and remained unchanged in the kidney structures. A decrease of mrp2 expression in renal tubules leading to a decrease of metabolic intoxication of the kidney was demonstrated in cholestasis of pregnancy model. In bile ducts cells, negative correlations of mrp2 with previously measured levels of prolactin receptors, CFTR, and mrp3 were revealed. In renal structures and in hepatocytes, no correlations were found between the expression of these proteins. We hypothesize that prolactin produces a direct effect on mrp2 expression in bile ducts cells mediated by prolactin receptors in cholangiocytes. The absence of correlations between mrp2 and the above-mentioned proteins in hepatocytes and renal structures is most likely related to prolactin effects on other systemic regulators.

Participation of Na+/K+-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na+/K+-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na+/K+-ATPase measured by Western blotting in the kidney medulla. Decrease in Na+/K+-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na+/K+-ATPase. There were no correlations between the Na+/K+-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na+/K+-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholestasis of pregnancy.

The effect of hyperprolactinemia on bile excretion from the liver of female rats was shown to increase significantly during obstructive cholestasis. The observed changes were biphasic: initial increase in bilirubin release of into the bile was followed by its reduction. Under conditions of obstructive cholestasis, hyperprolactinemia had a negative effect on the recovery of bile flow rate during decompression of the duct (up to complete cessation of bile flow).

Experiments on rats revealed sex-related differences in bilirubin concentration in the bile and bile flow rate against the background of obstructive cholestasis. These differences disappeared after gonadectomy. There were no sex-related differences in the rate of bilirubin excretion with the bile after removal of cholestasis, which was attained through different mechanisms in males and females.

Immunohistochemical study revealed overexpression of prolactin receptors in central and peripheral cells of intrahepatic grafts from H27 rat hepatoma without changes in compartmentalization compared to hepatocytes of intact animals. Experiments with gonadectomized animals showed that the hormonal regulation of prolactin receptors in both types of tumor cells does not differ from that in normal liver cells (positive estrogen-dependent regulation and negative androgen-dependent regulation).

The article presents an assessment of anticoagulant effect of rivaroxaban in 35 patients with thromboembolic diseases. The results of expressed anticoagulant effect of rivaroxaban were obtained during a day (or more). The data of increase in sensitivity to thrombomodulin indicated about work enchancement of protein C system against the background of rivaroxaban therapy.

The aim of the work was to study the role of cellular and humoral immunity in progression of myeloma disease (MD). The study included 97 patients and 125 age and sex-matched healthy volunteers. The state of cell-mediated and humoral immunity was evaluated at admission, before the pathogenetic treatment, by indirect immunofluorescence technique using anti-CD3, CD4+, CD8+, CD16+, CD19+, HLA-DR+ monoclonal antibodies. Serum IgA, IgM, IgE, IgG were measured by immunoenzymatic assay. The results were analysed using Statistica 7.0 (StatSoft, USA) program. The quantitative values are expressed as the median (Me) and interquartile range (C25-C75). Qualitative variables are presented as absolute values and percentage. The critical statistical significance level was taken as 0.05. The patients with MD developed combined secondary T, B-cell immunodeficiency. The disbalance between CD4+ cells and cytotoxic lymphocytes as well as signs of B-lymphocyte deficit increased with the progress of the disease. The number of NK-cells decreased at all stages of the disease. A rise in the serum level of LgC at all stages compared with control is an identifying sign confirming diagnosis of G-variant of myeloma disease.

The presence of prolactin receptor and peculiarities of its isoform expression in bile duct cells (cholangiocytes) differentially isolated from rat liver under different conditions were investigated in the present study. Normal cholangiocytes express prolactin receptor at relatively low level comparable to those of some prolactin-dependent tissues. Long receptor isoform is predominant in cholangiocytes but not in hepatocytes. The prolactin receptor level increases significantly under obstructive cholestasis due to evaluation of long and appearance of short isoforms. In rat cholangiocytes, unlike other tissues, the main positive regulators of prolactin receptor expression are cholestasis-induced factors instead of sex hormone and prolactin levels. Long isoform is predominant and induced primarily by cholestasis-induced factors.

The effects of obstructive cholestasis and sex hormones on the total content of prolactin receptor mRNA and ratio of mRNAs of its short and long isoforms have been studied in rat hepatocytes. Obstructive cholestasis caused insignificant changes in total content of prolactin receptor mRNA, but the proportion of mRNA of the long isoform increased. Comparison of prolactin receptor mRNA levels in gonadectomized and intact animals revealed opposite effects of male and female sex hormones on total mRNA, but both groups of these hormones increased the proportion of prolactin receptor short form mRNA. Changes in ratio of mRNA of receptor isoforms found in rat hepatocytes under obstructive cholestasis did not depend on levels of sex hormones. Obstructive cholestasis and sex hormones are suggested to regulate the content of long and short prolactin receptor isoforms in hepatocytes independently.

To compare the complex treatment of peritonitis with cryosupernatant and with fresh frozen plasma.Outcomes of treatment were studied in 88 patients receiving cryosupernatant and in 112 receiving fresh frozen plasma.Cryosupernatant application provides better dynamics of hemostasis, decreases a risk of thrombosis and mortality and improves outcomes of treatment.Cryosupernatant can be used instead of fresh frozen plasma in complex treatment of disseminated intravascular coagulation in patients with generalized peritonitis.

Immunohistochemistry with semi-quantitative analysis of computer images showed that prolactin receptor and cystic fi brosis transmembrane regulator (CFTR) in cholangiocytes of female rats elevated in cholestasis quickly respond to its relief. The effect of hyperprolactinemia on the extent of return of these proteins to baseline was different. Decompression of the bile duct abolishes the negative effect of hyperprolactinemia on CFTR expression and its positive effect on mrp3 expression in the proximal renal tubules. In renal medulla, mrp2 expression decreased when cholestasis was induced against the background of hyperprolactinemia and increases after its removal. Prolactin receptors and CFTR in cholangiocytes are most susceptible to the decrease in bile duct pressure. Changes in the expression of the studied proteins after cholestasis relief are apparently associated with attenuated toxicity of the products removed by the kidneys, which abolishes the effects of prolactin.

The article presents the data on the assessment of nutritional status, taking into account humoral immunologic criteria of patients with ulcerative colitis.

Generally recognized factor, which complicates the course of sepsis, is the development of hypercoagulation syndrome. The increase of thrombin coagulation indicates on the elevation of risk of thrombus formation in microcirculation vessels, which could cause the formation of multiple organ failure. The thrombin generation assay is a new method of the evaluation of homeostasis system status. The test reflects the fermentation activity of thrombin and shows the functional condition, which arises in the interaction of procoagulant and anticoagulant. The diagnosis of generalized peritonitis had 30 patients (18 men and 12 women, aged 61+/-18,3 years) and they were included in the research. It was shown, that the use of thrombin generation assay in patients with the abdominal sepsis could give the well-timed analysis of hypercoagulation changes and the assessment of protein C system investment in the thrombin generation.

This work is devoted to the study of the role of iron ions in the carcinogenic and mutagenic activity of chrysotile. For this aim natural chrysotile was treated with ferric chloride (III), washed, crushed and intratracheally introduced into Wistar rats. When administered to rats intact chrysotile induced mesotheliomas in 27,9 + 4,6% of cases, and chrysotile modified with ferric chloride - in 1,3 +/- 1,3%. Mutagenicity of the same samples was studied in the micronucleus test when administered intraperitoneally to mice Fl (CBA x S57Bl6). Polychromatic erythrocytes in the bone marrow were investigated 24 hours after intraperitoneal administration. The frequency of polychromatic erythrocytes with micronuclei was decreased from 7,4 +/- 0,18 by 1000 due to the action of chrysotile, from 2,8 +/- 0,42 for 1000 after the introduction of a modified sample. It is hypothesized that the ferric chloride modifies the surface of asbestos fibers that reduces the induction of free radicals which are the primary cause of and carcinogenic effects of chrysotile.

Immunohistochemistry with semiquantitative image analysis showed that cholestasis induced an increase in the manifestation of mrp3 in cholangiocytes of female rats, but did not affect this parameter in the studied structures of kidney. Under conditions of normal liver function, mrp3 expression in cholangiocytes was also elevated during hyperprolactinemia. Expression of mrp3 in cholangiocytes directly correlated with prolactin receptor expression. In cholestasis, prolactin increased mrp3 manifestation of only in the distal renal tubules. Thus, mrp3 manifestation increases in liver cells, but remains unchanged in kidney cells. The hyperprolactinemia-induced changes in the mrp3 levels and their correlations with prolactin receptor expression were shown to differ in the kidney and liver cells. It was hypothesized that prolactin produced a direct effect on mrp3 expression in cholangiocytes.

Disturbances of the erythrocyte antioxidant system presented by LPO intensifi cation were detected in patients with multiple myeloma. Plasma concentrations of MDA in these patients were close to normal due to effective work of the nonenzymatic antioxidant system. Activities of antioxidant enzymes in the plasma were reduced, while catalase activity was high, and ceruloplasmin content did not differ from the control, this indicating suppression of the enzymatic component of the antioxidant system. In erythrocytes, the level of reduced glutathione was low, especially at stage III of the disease. Changes in SOD and catalase activities were similar to those in the plasma, while activities of glutathione-dependent enzymes were comparable to those in normal human erythrocytes.

Abdominal sepsis (AS) is a systemic inflammatory reaction of organism in response to the development of infectious process in organs of the abdominal cavity. The course of AS is complicated by hypercoagulation syndrome which facilitates progression of endogenous intoxication. The investigation included 26 patients (14 men and 12 women, mean age 65.5 +/- 16.4 years) with AS. The test of thrombin generation (TTG) used in patients with AS allows assessment of changes in the hemostasis system and control of the heparin dose. It was established that TTG revealed elevated endogenous thrombin potential of blood practically in all patients with AS. In the patients given 25 000 IU of heparin the TTG indices showed a reliably decreased endogenous thrombin potential and peak thrombin concentration as compared with a group of patients given 10 000 IU of heparin.

We studied the possibility of prolactin involvement in the regulation of water-salt metabolism in female rats in the model of cholestasis of pregnancy. For simulation of the prolactin level during pregnancy, hyperprolactinemia was simulated by transplantation the pituitary under the renal capsule of the recipient; for modeling cholestasis of pregnancy, a combination of induced hyperprolactinemia and bile duct obstruction was used. Diurnal diuresis, expression of aquaporin 1-4 mRNA in the renal medulla, glomerular filtration rate, and diurnal sodium excretion were evaluated in these models. Diuretic and natriuretic effects of prolactin in the model of cholestasis of pregnancy were demonstrated. These data and the fact that prolactin has no effect on glomerular filtration rate and aquaporin expression suggest that prolactin modulates activity of sodium transporters in the kidney.

Immunohistochemistry with semiquantitative image analysis showed that prolactin receptor in distal renal tubules of female rats is most sensitive to the negative effects of both cholestasis and hyperprolactinemia. The responses of medullary tubules to cholestasis and hyperprolactinemia were less pronounced: decrease and increase in prolactin receptor expression, respectively. Proximal tubules were characterized by stable levels of prolactin receptor expression insensitive to the effects of obstructive cholestasis and hyperprolactinemia. The cholestasis-induced changes in the intensity of prolactin receptor expression were opposite in kidney and liver cells. It is concluded that different parts of the nephron differ by the presence, type, and direction of regulation of prolactin receptor expression in obstructive cholestasis and hyperprolactinemia.

The mechanisms of participation of multidrug-resistance proteins (MRPs) in sex difference pattern of drug efficiency and side effects have been analyzed. MRPs structure, their tissue and cellular localization, substrate specificity, and functions have been considered. Regulation of expression and activity of MRPs by endogenous metabolites, signal compounds, including sex hormones, as well as by drug agents have been represented. The role of nuclear receptors in the regulation of MRPs expression has been demonstrated. The data on sex differences in hepatic and renal MRPs expression and expression of nuclear receptors, participating in their induction, have been shown. The participation of MRPs in the formation of sex differences of drug pharmacokinetics has been discussed. Sex differences in representation and functional activity of MRPs in such excretory organs as liver and kidney was concluded would play the essential role in sex dependence of pharmacokinetics and efficiency of drug action.

During intraperitoneal administration of dispersiveness-comparable chrysotile or asbestos cement fibers to rats (20 mg thrice), mesotheliomas were found in 45.1 and 7.7% of cases respectively. Asbestos cement dust induced tumors in 2.5% of cases, which is of biological importance. Cement or freeze asbestos destruction cement dust failed to cause tumors. The latter were not detected in a control group receiving physiological saline. Asbestos cement fibers and fascicles are covered by a cement matrix. Fiber amorphization gradually occurs. In lung tissue, there may be destruction of the cement coat of fascicles and release of native chrysotile fibers that are carcinogenic.

A possibility of inheritance of androgen and basic genetic programs at the level of unusual estrogen-binding protein (UEBP) by daughter hepatocytes was investigated. Liver regeneration after partial ( 2 3 ) hepatectomy or after selective poisoning of hepatocytes of the central zone of hepatic lobules with CCl4 in adult rats were used as models of total and zonal proliferation of hepatocytes, respectively. UEBP content and the pattern of its tissue expression in the course of liver regeneration were monitored by radioligand and immunocytochemical technique. In animals of all groups possessing the androgen program of UEBP expression (intact, castrated and/or hypophysectomized males, and ovariectomized females treated with androgen) UEBP content was shown to be similarly high before initiation and after completion of liver regeneration. Unlike in males, in androgenized females a transient 4-fold increase of UEBP concentration on day 4 after partial hepatectomy was observed. In animals with a basic genetic program at the level of this protein (ovariectomized females, neonatally castrated males) only trace amounts of UEBP were observed in intact as well as in regenerated liver. The data were confirmed by immunocytochemical technique. A gradient mode of distribution of UEBP-contained cells within hepatic lobules with the highest specific staining around central veins was found by immunocytochemical technique in males. Specific staining of centrolobular and periportal hepatocytes was 7- to 10-fold in intact, and 4- to 6-fold in castrated and/or hypophysectomized males. In intact females specific staining was distributed uniformly at extremely low levels similar to that in periportal hepatocytes of males. Androgen administration to ovariectomized females stimulated a significant and stable increase of UEBP content in two layers of hepatocytes surrounding the central vein. Profiles of specific staining of hepatocytes within the hepatic lobules similar to that in control animals were observed after the completion of liver regeneration of different groups of rats. The results obtained suggest all the hepatocytes to be targets for androgen programming, natural in males or experimental in females, while the extent of expression of this program depends on the position of a hepatocyte within the liver lobules and the sex of the animal.

Gender-related differences in bilirubin concentration in post-cholestatic bile, bile excretion from the liver, and bile flow velocity disappeared in hyperprolactinemia in the presence of obstructive cholestasis. Gender-related differences in the alternative routes of bilirubin excretion appeared.

Wistar rats were fed propoxur in their diet at 0, 500, 3000, and 8000 ppm during throughout their life. The number of tumors was equal in the control and experimental groups. These were hemoblastoses and breast and uterine tumors. All tumors occurred spontaneously in the rats. A few experimental animals were found to have bladder epithelial hyperplasia that might be pretumorous; however, no bladder tumors were detected. It is concluded that the investigations revealed no carcinogenic activity of propoxur.

In spite of extensive research, no effective vaccine against hepatitis C virus (HCV) has been developed so far. DNA immunization is a potent technique of vaccine design strongly promoting the cellular arm of immune response. The genes encoding nonstructural HCV proteins (NS2-NS5B) are promising candidates for vaccine development. NS5A is a protein involved in viral pathogenesis, in the induction of immune response, and probably in viral resistance to interferon treatment. The objective of this study was to construct a DNA vaccine encoding NS5A protein and evaluate its immunogenicity. A plasmid encoding a full-size NS5A protein was produced using the pcDNA3.1 (+) vector for eukaryotic expression system. The expression of the NS5A gene was confirmed by immunoperoxidase staining of the transfected eukaryotic cells with anti-NS5A monoclonal antibodies. Triple immunization of mice with the plasmid vaccine induced a pronounced cellular immune response against abroad spectrum of NSSA epitopes as assessed by T-cell proliferation andsecretion of antiviral cytokines IFN-gamma and IL-2. In in vitro T-cell stimulation experiments, NS5A-derived antigens were modeled by synthetic peptides, recombinant proteins of various genotypes, and phages carrying exposed NS5A peptides. A novel immunomodulator Immunomax showed high adjuvant activity in DNA immunization. The data obtained indicate that the suggested DNA construct has a strong potential in the development of the gene vaccines against hepatitis C.

Regular intraperitoneal administration of peptone to rats was initiated immediately and 12 months after intraperitoneal thrice injection of crokidolite UICC in a dose of 20 mg. The rate of peritoneal mesotheliomas was 37.8% after co-administration of peptone and crokidolite, 25.6% following 12 months of crokidolite injection, and 72.1% after use of crokidolite alone. The effect of peptone administration is accounted for by the action of macrophages on transformed mesothelial cells and mesothelioma cells.

Comparative study of results of complex treatment of pancreonecrosis in 60 patients using cryosupernatant plasma (CSNP) and fresh frozen plasma was carried out. Better positive dynamics in some laboratory indices, less lethality and better outcomes were marked with use of CSNP. It can be used instead of fresh frozen plasma in complex treatment of pancreonecrosis and concomitant DIC syndrome.

In order to clarify the role of the central nervous system in the genesis of arterial hypertension (AH) a population analysis of somatic pathology in schizophrenia was performed. Using clinical and postmortem data, the study found lower frequency of AH among mental patients vs. somatic ones; primary AH was benign independently of the psychotropic therapy regimen. II to III stage AH in psychosis was associated with primary or secondary renal pathology or magistral vessel atherosclerosis. Severe schizophrenia and a pronounced personality defect were associated with low intensity of the primary form of somatic nosology.

A comparative analysis of the treatment of 120 patients after endoprosthesis for degenerative-destructive diseases of the hip joint was carried on. All the patients were divided into two groups: the main group included 74 patients who underwent a full course of rehabilitation, the control group consisted of 46 patients without rehabilitation. The results of a comparative assessment of the static-dynamic function in the two groups of patients after operation of endoprosthesis have shown the inclusion of an obligatory program of rehabilitation to be expedient for the restorative treatment in addition to the operation of endoprosthesis.

The study was made of carcinogenic efficiency of 4 GeV/nucleon helium ions (LET = 0.88 keV/um) in comparison with gamma-radiation 60Co (LET = 0.23 keV/um). Adult outbred female rats underwent a single whole-body irradiation with helium ions in doses 0.25-4.0 Gy at the Synchrophasotron of the Joint Institute for Nuclear Research and with gamma-rays at "PX-gamma-30" irradiator in doses ranged from 0.5 to 4.0 Gy. The yields, histology and occurrence time of hemoblastoses and tumours in mammary glands, in endocrine glands, in soft tissues and in other organs were determined. Histological study was made using conventional methods. The irradiation of experimental animals with accelerated helium ions and standard radiation was shown to result in an increase in the yield of growths of various localizations with decreasing occurrence time and expanding histological spectrum as compared with intact rats. However, helium ions possess a higher carcinogenic efficiency. The coefficients of relative biological effectiveness of helium ions calculated by the nonparametric method appeared to increase with decreasing the radiation dose.

Endothelial injury markers, including endothelial microparticles (CD31+ particles, 1.5-4.0 microm in diameter), von Willebrand factor, endothelin-big 1-38, and plasma concentrations of thiobarbituric acid reactive substances in patients with essential hypertension (EH), were evaluated. The endothelial injury markers and the concentrations of thiobarbituric acid reactive substances were significantly elevated in patients with EH, as compared to healthy subjects and decreased, so was blood pressure in response to antihypertensive pharmacotherapy. However, the patients and the healthy subjects had differences in these parameters. It is suggested that all the studied parameters of endothelial injury are suitable for laboratory monitoring of treatment in patients with EH in different periods of the disease, including a stable blood pressure period.

Morphofunctional features of skin mast cells located in the areas subjected to chronic UV-radiation and in the associated basal cell carcinoma with photoinjure have been studied. Various immunohistochemical methods (chromogranin A, CDla, HLA-DR, CD35, Ki67, P53, Bcl-2, Mcl-1, involucrine) were used. It is found that chronic UV-damage leads to mast cell hyperplasia as well as activation of their synthetic, absorption and secretory functions. It is suggested that mast cell hyperplasia and increase of mast cells neuroendocrine activity provide a risk of basal cell carcinoma development.

Data available on the pathways of asbestos (fibrous) carcinogenesis still leaves much to be desired. Asbestos is regarded as a non-genotoxic substance by most researchers. There is insufficient evidence on the interaction of fibres, target-cells and macrophages. Macrophages secreted proteins (ca. 450 kD) to inhibit proliferation of intact mesothelium and cytoxine (3-5 kD) which stimulated the cellular sensitivity of intact mesothelium and mesotheliomas to the toxic influence of asbestos. It was suggested that the effect was due to the triggering of intrinsic causation of cell death. Like any other fibres, carcinogenic effect of asbestos could be accounted for by such significant factor as active oxygen radicals. When exposed to asbestos, both intact mesothelial and mesothelioma cells and macrophages synthesized those substances. Free radical-like substances in conjunction with macrophage-conditioned media produced toxic effect on mesothelial cells. The role of active oxygen radicals in fibre-induced carcinogenesis is discussed.

The arrangement and ultrastructure of rectal intraepithelial endocrine cells in health, in nonspecific ulcerative colitis (NSUC) and in irritable colon syndrome (ICS) were studied with light and electron microscopy. An increase of the amount of these cells was registered at the initial stages of inflammation, whereas chronic and destructive states were accompanied by the cells decrease. A decrease of endocrine cells number in (NSUC) was pronounced more than in ICS. Compared to prednisolone, the treatment with salofalk produced a more positive effect on endocrine cells reproduction within the rectal lining. The endocrine cells ultrastructural changes found by the authors in ulcerative colitis and irritable colon showed similarity to those in other colon diseases.

Indirect immunoperoxidase assay and computer analysis of photographic images revealed more intensive expression of prolactin receptors in hepatocytes of women compared to men. The intensity of expression was maximum in secondary liver cancer, high in obstructive jaundice of different etiology, and less pronounced in cholelithiasis. The expression of prolactin receptors in cholangiocytes was higher than in hepatocytes and was maximum during obstructive jaundice of different etiology. Cells of secondary tumors were characterized by low expression, while distant hepatocytes most intensively expressed prolactin receptors.

A 15-year-old patient has been admitted to the intensive care unit for severe respiratory distress syndrome that developed as a result of pneumonia. Interstitial lung edema was confirmed by computer-aided tomography. It was successfully treated by positive pressure ventilation (PPV). Although PEEP did not exceed 7 cm H2O, PPV was complicated by interstitial emphysema, pneumomediastinum, and bilateral pneumothorax as a result of barotrauma. Pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP) were monitored. High PCWP values were inconsistent with the diagnosis of acute respiratory distress syndrome. The authors suggest that high PCWP was caused by high intraalveolar pressure, pneumomediastinum, and venule constriction in the hypoxic sites of the lung.

Using the technique of immunohistochemistry in combination with cytophotometry, we have studied the effect of periovulatory hyper- and hypoprolactinemia on the expression of prolactin receptors in various cell types of rat ovaries during early estrus. It has been shown that intense specific staining of oocytes is positively controlled by prolactin. The maximal intensity of specific staining was found in cells of the cumulus and the inner layer of granulosa cells in mature follicles; staining intensity gradually diminished towards the outer boundary cell layer. Postovulatory follicles are distinct from those mature follicles in which there was no ovulation in their more intense manifestation of prolactin receptors in cells of the inner layer and cumulus, as well as in increased positive staining (after prolactin administration) only in the granulosa layer cells closest to theca. In follicles which did not ovulate by the time of the early estrus, prolactin administration leads to a proportional growth of specific immunoreactivity in all cell layers of the granulosa. The administration of bromocryptin, an inhibitor of prolactin secretion, leading to a 10-fold decrease in prolactin level in blood, results in a twofold decrease in the intensity of specific staining of all cell layers of the granulosa in either type of follicle. Corpora lutea of the previous cycle have irregularly positioned luteocytes with weak and strong specific staining, the intensity of which is not changed in response to prolactin and diminishes slightly after the administration of bromocryptin. We conclude that the most intense changes in the content of prolactin receptors under the conditions of imbalance of this hormone during the periovulatory period are observed in those follicles where the oocyte did not ovulate by the time of early estrus.

Indirect immunoperoxidase technique in combination with cytophotometry showed that prolactin imbalance in the periovulatory period is characterized by considerable changes in the expression of prolactin receptors in uterine glands and endometrial stroma (but not in the myometrium) and in the pituitary gland and hypothalamus, while receptor compartmentalization pattern remaines unchanged.

Mouse and rabbit preimplantation embryos with intact zona pellucida were incubated for 3 hr with DNA-carrying constructs containing insulin as an internalizable ligand: (insulin-polylysine)-DNA and (insulin-polylysine)-DNA-(streptavidin-polylysine)-(biotinylated adenovirus). Video-intensified microscopy demonstrated that the constructs penetrated the zona pellucida and accumulated in the blastomere perinuclear space. The percentage of blastocysts formed was about 70% after incubation of zygotes and two-cell embryos with the constructs. Foreign DNA was detected after 51 hr in 80% of rabbit embryos and after 96 hr in 73% of mouse embryos. Inclusion of various adenoviruses into the construct improved foreign DNA preservation in early embryos. Blot hybridization revealed genome-integrated foreign DNA in 12- and 15-day mouse embryos and in a newborn. Thus, the ligand-mediated mechanism can be employed for introducing foreign genetic material into early mammalian embryos; insulin provides for delivery inside the cell and to the nucleus, while adenoviruses ensure release from endosomes.

To investigate the effectiveness of superfrequent transesophageal left atrial stimulation (TLAS) and its combination with cordarone in management of atrial flutter (AF).650 patients with paroxysmal AF underwent TLAS. The paroxysm duration varied from 1 hour to 1 month. In 312 patients TLAS was performed prior to treatment with antiarrhythmic drugs (group 1), in 338 patients--after intravenous administration of cordarone (group 2).Superfrequent TLAS has restored sinus rhythm (SR) in 85(27.2%) and 169(50%) patients of groups 1 and 2, respectively (p0.001). TLAS promoted conversion of AF in atrial fibrillation (AFi) in 185(59.3%) and 159(47.1%) patients of groups 1 and 2, respectively (p0.01). Moreover, SR recovered 24-48 hours after TLAS in 87(27.9%) and 64(18.9%) patients of groups 1 and 2 respectively (p0.01). Sinus rhythm recovered in a total of 172(55.1%) and 233(69.0%) patients, AF was converted to AFi in a total of 88(31.4%) and 95(28.1%) patients (p0.05) of groups 1 and 2, respectively. TLAS was uneffective in 42(13.5%) and 10(2.9%) patients of groups 1 and 2, respectively.Superfrequent TLAS is a highly effective and non-invasive modality in the treatment of paroxysmal AF. It promotes recovery of SR. In some patients TLAS induces AFi which is more controllable by medication as regards the heart rate. Cordarone contributes to the response to TLAS in patients with paroxysmal AF.