[Influence of various bacterial ligand application methods on cytokine expression].

AIM: Study the production of cytokines in mice during vaccination with polycomponent Immunovac-VP-4 vaccine containing TLR ligands with various administration methods. MATERIALS AND METHODS: Immunovac-VP-4 was administered to mice by subcutaneous, intranasal or per oral methods. The preparation was administered nasally at a single dose of 500 microg in the volume of 30 microl. Per oral single dose was 2000 microg in the volume of 0.5 ml. 200 microg of the preparation was administered subcutaneously. Cytokines in blood sera were determined by EIA 8 hours after the administration of the vaccine. RESULTS: In mice 8 hours afterthe single administration of Immunovac-VP-4 the levels of IL-1beta, IL-6, IL- 12, IL-5 increased significantly. However their concentration differed depending on the method of administration. The most active expression of cytokines was observed during subcutaneous administration. The indexes of cytokine expression were significantly higher (p < 0.05) than during non-parenteral administration methods. CONCLUSION: Mucosal application methods along with parenteral were established to be able to activate effector mechanisms of immune repose with its consequent polarization by Th1/Th2 pathways. These mechanisms lay the groundwork for development of antigen-specific immune responses against antigens/pathogens.

[The characteristic of immunity in long-lived persons and selection of the immunosenescence markers].

Purpose of the work is to select the indices of immunograms, associated with immunosenescence. The lymphocyte subpopulations were defined by the method of polychrome flowing cytometry in 276 patients of 90+ year with the identical spectrum of chronic unspecific inflammatory diseases. The cluster was revealed consisting of subpopulation of T-lymphocytes (T-lymph) with the high frequency of deviations from standard--helper CD4+, cytotoxic CD8+--T-lymph. The activation of immunity was confirmed by the expression of HLA-DR molecule in 100% of persons with an increase of the absolute number CD4+ and/or CD8+. Reduction in the CD8+ and/or CD4+ was associated with the immune deficient state and the frequency of the increased actTcontent within limits of 63-83%. In 36 long-livers a quantity CD4+ and CD8+ corresponded to standard, 33 of them demonstrated actT exceeded standard. These patients were carried to the group of activation also. Basic group had the quantity CD8+ deficit (73%). In this group, frequency of the development of neuro-degenerate distributions and pathologic changes in the osteomuscular tissue were reliably higher in the persons at the age of 92 years and older than in persons younger 92 years. We consider that CD8+ deficit at the age older 90 year is biomarker of immunosenescence and the risk of an increase in the frequency of development of chronic unspecific inflammatory diseases.

[Assessment of clinical and antiaggregation efficacy of generic clopidogrel 'Egithromb' in roentgenosurgical practice].

The authors studied efficacy of the generic clopidogrel Еgithromb manufactured by EGIS PHARMACEUTICALS (Hungary) based on clinical data and parameters of light aggregometry in a total of 30 patients subjected to planned subcutaneous coronary intervention for stable angina pectoris. It was noted that the generic clopidogrel Egithromb possesses clinical efficacy, manifesting in the lack of early thromboses of the stents and relapses of angina pectoris during the first month of treatment. The findings obtained by light aggregometry strongly suggested a significant decrease in aggregation with a dose of ADP 1.25 mcg/ml in 87.33% of patients, with the target values of the index less than 25% were obtained in 100% of cases. It was determined that the agent possesses high efficacy in aspirin-resistant patients and in the presence of thrombinemia. There were neither side events of therapy nor haemorrhagic complications in the present study during treatment.

[The role of gastric pH and tissue hypoxia in formation of gastroduodenal zone mucose changes in heartsurgical patients].

The estimation of gastric contents pH and gastroduodenal zone mucous membrane condition based on the fibrogastroduodenoscopy data of40 patients who were examined and received proton pump inhibitors in the postoperative period after heart surgical intervention. It was estimated, that acidic peptic aggression and tissue hypoxia are important factors for occurrence of destructive gastroduodenal membrane changes in heart surgery patients. The differences of antisecretory activity of proton pump inhibitors are revealed, so it was useful to use analogous pH-test using in the intensive care unit. The preferences of original omeprazole for intravenous use with it antisecretory effect were marked in comparison with generic omeprazole: the stability of gastric contents pH more than 4,0 was in 100%, more than 6,0 was in 86% of the time for original drug and in 84% and in 27% for generic drug respectively. It is also demonstrated, that cardiotonic drugs using and prosthesis of cardiac valves are additional risk factors of gastroduodenal membrane destruction, independent of acidic aggression.

[A combined method to protect the brain during operations on the brachiocephalic arteries].

Based on the outcomes of surgical management of thirty-six patients diagnosed with atherosclerosis of carotid arteries and a further thirty-five 35 patients presenting with atherosclerotic lesions of the subclavian and vertebral arteries the authors substantiated a differentiated therapeutic policy aimed at protecting the brain from ischaemia, having demonstrated efficiency of cerebral protection with nimodipine and rheopolyglukin in patients subjected to operations on the subclavian and vertebral arteries and feasibility of combining this method with the application of a temporary puncture carotid-artery bypass graft during carotid endarterectomy. Functional possibilities of puncture-mediated bypass grafting of the carotid artery was confirmed by studying the blood flow in the common, internal carotid and median cerebral arteries on the operated side and ipsilateral side in patients with and without a bypass graft applied.

[Diagnosis and treatment of cystic forms of duodenal dystrophia].

Cystic dystrophy of duodenal wall and duodenal dystrophy (DD)--is a rare disease which is based on chronic inflammation of the pancreas tissue (PT), malrelated in the wall of the duodenum (DU). The principal method of surgical treatment of this disease is Pancreaticoduodenectomy (PRD), although it was presented several reports of successful use sandostatin or endoscopic treatment in some patients. Analysis of demographic, clinical and instrumental data, methods of surgical treatment of DD showed that all patients with persistent or recurrent abdominal pain was noted in all patients, weight loss--51%, vomiting--at 26%, jaundice--in 20% of patients. The most accurate diagnostic methods were CT, endo-ultrasound and MRI. The diagnosis of duodenal dystrophy installed in 35 patients. Operations were performed on 22 patients: Implemented PRD (10), removal of pancreatic head resection with a vertical branch of the PT and duodenoduodenoanastomosis (2), pancreatic head resection with excision of the cyst wall of the first portion of duodenum (2), gastric resection (1), resection of the vertical branch of the duodenum with duodenoduodenoanastomosus (2), duodenectomia (1) and resection of the vertical branch of the duodenum with reconstruction of the intestinal insert (2). Four patients fulfilled draining intervention on pancreatic ductal system--pankreatico and cystoenteroanastomoses. Postoperative and late mortality--0.77% of patients the disappearance of pain and 23%--a decrease in its intensity. In two cases, after the PRD against the background of pronounced chronic pancreatitis observed impaired glucose tolerance. Cystic dystrophy of duodenal wall without the expressed "orthotopic" pancreatitis clearly shows pathogenetic, clinical, diagnostic and therapeutic aspects of this disease, causing the possibility of an effective surgical treatment, only limited intervention by the KDP, without resection of the pancreas.

[Assessing clinical efficacy of the generic clopidogrel "Egutromb" in roentgenosurgical practice].

The study comprised a total of ten 47-to-62-year-old (mean age 52.8±2.05 years) patients presenting with coronary artery disease. All patients underwent coronography whose findings were used to determine the indications for stenting of coronary arteries in order to correct coronary insufficiency with due regard for the international guidelines. All the patients received therapy with acetylsalicylic acid at a dose of 75-125 mg/day. As preoperative preparation in all cases the patients were given the generic clopidogrel Egitromb at a daily dose of 75 mg given 120 hours (5 days) prior to the intervention. The clinical effect of the drug was assessed by the presence or absence of relapses of cardiac angina, or the development of acute coronary syndrome within 1 month following the endovascular intervention performed. The state of the vascular-thrombocytic haemostasis was evaluated by the following parameters: spontaneous blood platelet aggregation, induced by ADP given at a dose of 5 µg/ml and 1.25 µg/ml. The obtained initial positive findings of studying clinical efficacy of the generic clopidogrel "Egitromb" manifesting itself in the absence of early stent's thromboses and relapses of cardiac angina within the first month of treatment, as well as in a significant decrease of induced blood platelet aggregation with ADP at a dose of 5 µg/ml and 1.25 µg/ml suggest the necessity of continuing further study thereof in roentgenosurgical practice.

[Stress-dependent lesions of the gastroduodenal mucosa during operations with cardiopulmonary bypass].

A continuous retrospective study was conducted in order to reveal risk factors and optimal ways of prophylaxis of gastroduodenal hemorrhage after operations with cardiopulmonary bypass. All the 559 cases operated on with cardiopulmonary bypass in Department of Cardiosurgery of Omsk Regional Clinical Hospital between January 2003 and December 2005 were analyzed. Risk factors and the effectiveness of different methods of antisecretory prophylaxis of hemorrhage were evaluated. It was found that the frequency of postoperative gastroduodenal hemorrhage was influenced by the degree of circulatory insufficiency, duration of artificial lung ventilation, cardiopulmonary bypass, and aortal occlusion, as well as application of anticoagulants and the frequency of gastric and duodenal erosions or ulcers prior to operation. The most effective means of prophylaxis was omeprazole administered intravenously during three days followed by oral application during three weeks. A short course of H2-histamine blockers discontinued abruptly increased hemorrhage-related lethality in this group of patients due to withdrawal syndrome.

[Peptic ulcers of the gastroduodenal zone in patients with scheduled cardiac operation: continuum of heterogeneous pathogenetic effects].

The article is a review of different pathogenetic mechanisms (infectious, NSAID-associated, stress-dependent and those stipulated by microcirculation disturbances in the gastroduodenal zone) of stomach and duodenum ulcers in patients with scheduled surgical intervention on the heart with the use of cardiopulmonary bypass. Some vexed questions related to treatment tactics of peptic ulcers in these patients are discussed.

[Immortalized cell lines from murine embryos are characterized by progressive destabilization of their karyotype structure]. / Immortalizovannye linii kletok, poluchennye iz transgennykh émbrionov myshei, kharakterizuiutsia progressiruiushzchei destabilizatsiei struktury kariotipa.

The karyotype structure was studied for three cell lines obtained from cells of transgenic murine embryos at early stages of their establishment. The first line was obtained from a transgenic embryonic explantant containing oncogen v-sis under promotor MMTV, two other lines originated from cells of transgenic embryos containing oncogen k51. The karyotypic analysis of G-banded metaphase chromosomes revealed deviations from the normal mouse karyotype as early as by the third passage of cultivation of independent embryonic cell lines that contained a foreign oncogene in their genome. The repeated analysis that involved 15-22 passages revealed similar abnormalities: variability and progression in chromosome number with the appearance of hyperpolyploid combinations, and a large number of rearranged chromosomes, both marker and unique ones. It is concluded that introduction of a foreign oncogene into murine cell genome leads to its enhanced and progressive non-specific destabilization. Oncogen v-sis produces a more valuable karyotype destabilization than oncogen k51.

[Anatomical and physiological foundations of the chronic hemorrhoids formation and prospects of their surgical and conservative treatment]. / Anatomo-fiziologicheskie osnovy formirovaniia gemorroia i osobennosti ego lecheniia.

Anatomical and physiological aspects of the chronic hemorrhoids formation with a detailed description of physiopathologic mechanisms at this disease have been stated. Up-to-date aspects of surgical treatment with the assessment of positive and negative points of each method have been e analyzed. Prospects of the complex conservative treatment are given based on many-sided pathogenesis aspects.

[Visceral hypersensitivity of the large intestine mucosa in patients with irritable bowel syndrome--cause of the non-inflammatory changes in the pain syndrome]. / Vistseral'naia giperchuvstvitel'nost' slizistoi obolochki tolstoi kishki u bol'nykh sindromom razdrazhennogo kishechnika--prichina nevospalitel'nykh ee izmeneniii bolevogo sindroma.

The purpose of our research was to reveal the existence of an association between clinical expressions of visceral hypersensitivity--the intensity of abdominal pain and nature of endoscopic changes in the large intestine in patients with the irritable bowel syndrome (IBS). It was established that there was a direct association between the intensity of the pain syndrome and existence of endoscopic changes in the large intestine mucous coat. The macroscopic picture regarded as an inflammation of the mucous coat in patients with the IBS is not confirmed with the data of morphological research. The presence of endoscopic features of inflammation is not favorable from the prognostic point of view for deletion of abdominal pain in patients who undergo therapy with selective antagonists of calcium.

[Current views of the pathogenesis of irritable bowel syndrome]. / Sovremennye predstavleniia o patogeneze sindroma razdrazhennogo kishechnika.

Three main trends in pathogenesis of irritable bowel syndrome are considered: dysfunction of psychic activity with associated changes in vegetative functions and humoral reactions, visceral hypersensitivity, abnormal intestinal motility. Morphological manifestations of the syndrome are also outlined.

[Humoral factors (beta-endorphin and adrenocorticotropin) in irritable bowel syndrome and their relations with psychological disorders and characteristics of disorders in the large intestine motility]. / Gumoral'ny efaktory (beta-éndorfin i adrenokortikotropin) pri sindrome razdrazhennogo kishechnika i ikh sviaz' s psikhicheskimi narusheniiami i kharakterom narushenii dvigatel'noi funktsii tolstoi kishki.

The object of this study was to discover mental functions, humoral regulation and large intestinal motor dysfunction in patients with the irritable bowels syndrome (IBS) in order to develop principles of their differential correction. A group of 106 patients (26 men and 80 women) with the irritable bowels syndrome was examined. The IBS diagnosis was made in accordance with the Rome criteria (1999). The control group included 21 somatically healthy volunteers (16 women and 5 men). Patients from both of the groups underwent clinical and psychological as well as plasma beta-endorphin concentration studies; colonic motor activity was also studied in patients with the IBS by the method of electric colonoscopy. Mental changes and certain particular features of the large intestine humoral regulation and motor activity determining the differential treatment for this category of patients were discovered.

[Effect of bemethyl on cytochrome P-450-dependent monoxygenases in the human liver and lymphocytes]. / Vliianie bemitila na tsitokhrom P-450-zavisimye monoksigenazy v pecheni krys i limfotsitakh cheloveka.

Effects of the actoprotector bemithyl (50 mg/kg, p.o.) upon a single or five-fold administration on the cytochrome P-450 and b5 content and the isoform-specific and nonspecific monooxygenase activity [aminopyrine-N-demethylase, aniline-p-hydroxylase, 4-nitroanisole-o-demethylase,2,5-diphenyloxazole-p-hydroxylase, 7-ethoxyresorufin-o-deethylase (EROD), benzyloxyresorufin-o-debenzylase (BROD)] in rat liver were evaluated. In addition, the influence of bemithyl (0.(1)-100 microM) on the development of EROD and BROD activity was studied on the mitogen-stimulated human lymphocytes in vitro. Administered in rats, bemithyl exhibited the properties of a cytochrome P-450 inductor of the mixed type, which was manifested by an increase in the total cytochrome P-450 content in liver microsomes and in the monooxygenase activity related to both Ah-receptor-dependent and -independent isoforms (except for the aniline-p-hydroxylase activity). The induction of the monooxygenase activity realized by Ah-receptor-dependent isoforms (4-nitroanisole-o-demethylase, 2,5-diphenyloxazole-p-hydroxylase, and EROD activity) was more pronounced, reaching maximum upon a single drug administration. Acting upon the human lymphocytes in vitro, high concentrations of bemithyl increased expression of the EROD activity, while low drug concentrations stimulated the BROD activity.

[Chaotic nonlinear dynamics of prestimulus EEG and the structure of auditory evoked potentials ]. / Khaoticheskaia nelineinaia dinamika prestimul'noi EEG i struktura slukhovykh vyzvannykh potenthialov.

The dynamic pattern of a prestimulus EEG was studied by the fractal analysis technique. The character of this pattern was shown to affect the structure of cortical auditory evoked potentials (EP). A monoperiodic pattern in the control frequency band was accompanied by a formation of several new attractors with low dimensionality attributed to simultaneous functioning of several weakly connected dynamic systems with an indefinite trend of a leading process. During development of multiperiodic processes in EEG segments, the fractal analysis revealed a tendency for a formation of a single complex dynamic system with high dimensionality of the attractor. Characteristic changes in parameters of the primary and middle-latency EP components, their correlation, and factor models are related with the character of nonlinear patterns. Analysis of variance revealed the most effective role of pattern changes in the EEG alpha control band. The structure of combination of parameters of the EP primary components into connected complexes depends on the nonlinear prestimulus EEG patterns. The above predictors determine differently directed and differently pronounced changes in parameters of the middle-latency positive waves.

Cloning and preliminary characterization of a calcium-binding protein closely related to nucleolin on the apical surface of inner medullary collecting duct cells.

Calcium stone crystal attachment to the urinary epithelium plays an essential role in the development of kidney stones by allowing small crystals to be retained in the kidney until they become macroscopic. We among others have described attachment of stone crystals to cultured renal epithelia (Wiessner, J. H., Kleinman, J. G., Blumenthal, S. S., Garancis, J. C., and Mandel, G. S. (1987) J. Urol. 138, 640-643). To isolate protein(s) that may participate in crystal attachment, apical membranes of cultured renal inner medullary collecting duct were biotinylated, the cells were lysed with detergent, the lysate was subjected to hydroxyapatite chromatography, and fractions were incubated with calcium oxalate monohydrate. Electrophoresis of material solubilized from the crystals showed several selectively adsorbed protein bands. A 110-kDa band stained positively for biotin and for glycosides and bound (45)Ca. The amino acid sequence of this band was determined to be that of a protein closely related to rat nucleolin (nucleolin-related protein; NRP). NRP was cloned and sequenced and was 83% homologous with the previously sequenced nucleolar protein nucleolin. Using temperature-induced phase partitioning with Triton X-114, NRP was associated with both the insoluble membrane skeleton pellet and the soluble aqueous phase but not the soluble detergent phase. This association with the membrane skeleton was increased in the presence of calcium. Thus, NRP is associated with the apical membranes of cultured renal tubular cells and is bound to membrane skeletal elements in a calcium-dependent fashion. The physiological role of NRP remains to be determined; however, a pathophysiological role may be that of mediating the attachment to the renal tubular epithelium of calcium stone crystals.

Resistance to adriamycin in human chronic promyeloleukemia line K562 correlates with directed genome destabilization--amplification of MDR1 gene and nonrandom changes in karyotype structure. / Ustoichivost' kletok khronicheskogo promieloleikoza cheloveka linii K562 k adriamitsinu korreliruet s napravlennoi destabilizatsiei genoma--amplifikatsiei gena MDR1 i ne sluchainymi izmeneniiami v strukture genotipa.

Three independent subclones (B2, B3 and C9) of human myelogenous leukemia cell line K562 selected with adriamycin (ADM) were analysed. Cross-resistance of these ADM-resistant cells was examined for a resistance to the number of drugs including colchicine, actinomycin D and ethidium bromide. MDR 1 gene amplification in B3 and C9 subclones was detected using Southern-hybridization with specific probe. Additional genetical material was found in genomes of resistant cells by analysis of G-banded metaphase chromosomes. An extraordinarily long marker chromosome was observed in every C9 metaphase plate. The character of this chromosome G-banding suggests that it may be a derivative of chromosome 5 containing a large homogeneously staining region (HSR) in locus 5q15. Both B2 and B3 subclones expressed double minute chromosomes (DMs) in 5% of cells. In the course of a prolonged cultivation (about 2 years) of C9 cells in the presence of ADM a progressive karyotype destabilization was observed: the frequency of new markers formation in C9 cells increased, cells having additional copies of marker chromosome with HSR appeared, the length of HSR varied, coexistence of HSR and DMs being found in several C9 cells. These karyotypical changes may be regarded as patterns of genome destabilization due to the multidrug resistance of K562/ADM cells.