Vol 4, No 1 (2004)

It is generally accepted that regulatory olygopeptides (RP) cause short- term physiological effects. Several approach to long term action of RP are reviewed in the article: 1) the segregation of new family of very stable RP, glyprolines, 2) the usage of glyprolines for stabilization of other endogenous RP, 3) the reveal of postponed effects of some RP, 4) the development of immunological methods for realization of very long- lasting activities of RP. In particular it was established that CCK-4 (Trp-Met-Asp-Phe-NH₂) and CCK-3 (Met-Asp-Phe-NH₂) evoked significant changes in albino rat behavior ( high anxiety, elements of depression) and bioamines levels not only at the first hours after administration but also on the 5th and even 12th days. The half life time of these peptides is less than 15 min. Therefore the induction of some chain-reactions similar to memory consolidation process is possible. On the other hand CCK-3 as well as CCK-4 covalently linked to antigen-carrier has evoked a long-lasting (at least during two months) inverse effects - suppression of the anxiety, decrease of depression-like behavior and diminishing of bioamines and their catabolites levels in striatum. It is a perspective approach to the problem of pathological anxiety and depression treatment.

The state of the oxidant - antioxidant system was studied in 80 patients: 25 patients were with moderate hemophilia and 55 patients with severe hemophilia. Some lipid peroxidation parameteres - the contents of diene and triene conjugates, malonyl dialdehyde in blood serum, as well as antioxidant system - the activities of superoxide dismutase, glutathione peroxidase, catalase, the contents of ceruloplasmin and nonprotein thiole groups demonstrating the level of reduced glutathione, were estimated. It was shown that the formation of lipid peroxides has not been balanced by the functioning of antioxidant system. The latter is being particularly aggravated in severe hemophilia. Approximately 2-fold elevation of lipid peroxidation products was noted together with the decrease of glutathione peroxidase activity, the contents of reduced glutathione and ceruloplasmin in recurrent bleedings. The above is confirmed by the alteration of the activity of superoxide dismutase and catalase: 3-fold decreased SOD/CAT coefficient in comparison with normal. The role of «oxidative stress» in pathogenesis of hemophilia and the significance of correction of antioxidant status by means of introducing the antioxidant remedies for treating hemofiliac patients is being discussed.

The main goal of the present study was to evaluate the genetic impact of some genes operating in coagulation system in the development of the inherited predisposition to myocardial infarction (MI) in young men before 45 year old. For this purpose, we investigated the allele distribution of the 7 following genes: F V Leiden, F2 G20210A, G/A-455 FGB, GP IIIa PIA1/A2, A1/A2 5’F7, 4G/5G PAI-1, C677T MTHFR. The significant prevalence of PIA2 GP IIIa frequency in the patients with MI compared with controls was found (16,2% and 9,8%, respectively, p<0,05). The allele frequencies of other investigated genes were not different in patients and control group. This results allowed us to make a conclusion that the inherited predisposition to MI depends on platelet function whenever the clotting factors have a little impact on genetic predisposition to MI in young men before 45 year old.

One of the basic mechanism taking part in atherosclerosis formation is immune-mediated inflammation of the vascular wall. The inflammatory cytokines have a significant role in this process. We established serum concentration of IL-1β, IL-2, IL-6, IL-8, TNF-α and expression of mRNA IL-1, IL-2, IL-6 in vascular wall of patients with coronary atherosclerosis. The serum levels of IL-1β, 2, 8 in patients with angina pectoris were found to be significantly higher than in healthy controls (0,45±0,08; 9,1±1,6; 94,2±27,6 pg/ml и 0,14±0,09; 0; 3,3±0,09 pg/ml, accordingly). The identification of IL-1β, IL-2, IL-6 in tissue revealed that radial artery wall contains mRNA of searched cytokines. The main cytokine of aorta appeared to be IL-2 (7 samples of 8), and the main periphery artery cytokine turned out to be IL-1β, IL-6 (5 samples of 8). Data obtained allows to make the following conclusions: increase of serum concentrations of IL-1β, IL-2, IL-8 in patients with angina pectoris reflects immune-inflammatory nature of the disease; detection of dissimilar cytokines in tissue sampling reflects not only different grade of vessel involvement in process but also phase evolution of the disease.

A total of 293 Mycobacterium tuberculosis strains isolated in the North-West of Russia in 1996-2001 from 148 newly diagnosed and 135 chronic patients with pulmonory tuberculosis were characterized by spoligotyping and IS6110-RFLP. The Beijing genotype strains, as defined by spoligotyping, were isolated from 53.9% of patients. The number of clustering strains with identical IS6110-RFLP patterns among Beijing strains was 2.3 (3.2 in new cases) folds more compared with non-Beijing strains. Drug resistant were 91.5% of Beijing strains and 78.5% of non-Beijing strains; multidrug resistant - 64.7% and 47.4% strains, respectively. Intravenous infection of mice showed high or medium levels of virulence in 64.7% of Beijing strains (n=29) versus 38.9% of non-Beijing strains (n=26). Beijing strains induced in patients more significant intoxication, extensive pulmonary lesions and progress of the desease compared with strains of other genotypes. Low efficacy of anti-tubercular therapy in patients infected with Beijing strains determined the necessity of pulmonectomy in 90% of those subjected to surgical treatment. After surgery such patients had frequent complications and high mortality.

Karyotypes of peripheral blood lymphocytes of the patients with chronic HCV infection were investigated. The increased frequency of chromosomal aberrations in comparison with the control group, dominant regions of chromosomal injuries and clonal character of aberrations find in several patients are established.

The data find are discussed according to the literature data on extrahepatic persistence and replication of HCV, probability of peripheral blood immunocompetent cells damage by HCV, and link of HCV persistence with a series of haematological syndromes and lymphoproliferative diseases.

In conclusion, the cytological investigation of patients with chronic HCV infection is proposed for advanced diagnostics and are prognosis of the disease.

The article bases on the results of empirical research in the Novgorod State University and discusses some issues of methodology and measurement techniques in the medical-sociological studying public health of the students. It reveals social-psychological grounds of the population’s self-appraisal of health and its relevancy to in health monitoring studies. Authors found deep discrepancies in the social-medical self-identifications by different groups of youth populations in the region. A contradicting connection in between the students’ health self-appraisals and their self-identifications by the scale of «a healthy man» is discussed as well as dynamics of these parameters by a number of social status indicators and duration of study in the University.

This review has been intended to illustrate mechanisms of pharmacological intervention on the immune system in so far as that is possible with the range of drags currently available. In immunopathological and inflammatory processes there are several possible points of intervention with drugs. Immunosupressive drugs are used in the management of organ and bone marrow transplantation and the treatment of diseases with proven autoimmune aetiology. Immunosuppressive agents (cyclophosphamide, azathioprine, glucocorticoid (GC) hormones) represent prototypic clinically relevant drugs. GC hormones have assumed a major role in the treatment of a variety of deseases with an inflammatory or immune-mediated components. The steroid and non-steroidal anti-inflammatory drugs provide good examples of drug which modify mediator release. Particularly important is the action of GC on cytokine production. This effect is dependent upon inhibition of gene expression in immunocompetent cells. Interest has been developing recently in the use of antibiotic cyclosporine for the treatment of rheumatoid arthritis, chronic inflammatory bowel disease and other autoimmune diseases. The discovery of a new immunosuppressant - macrolide antibiotic FK 506 also added much excitement. The both block antigen-induced transcription of the IL-2 gene in T-cells. Increasing knowledge of the role of cytokines in the regulation of the immune response, and availability of large quantities of recombinant cytokines, is focusing attention on their potential as immunomodulators for attempts at controlling immunity and inflammation. Cytokines are used as targets and sources for novel immunoregulators. Recent development of novel approaches to immunomodulation (monoclonal antibodies, cytokine antagonists) are considered briefly.