Vol 8, No 2 (2008)

In contrast to the prevailing viewpoint, monogenic disorders are responsible for many widespread pathologies not only in children, but in adults as well. Studies of monogenic diseases provided an invaluable contribution to our current knowledge of the genetic basis of such common multifactorial diseases as atherosclerosis, cancer and mental disorders. Moreover, studying genes and proteins with a function altered in monogenic diseases allowed developing new drugs now widely used for treatment of multifactorial and polygenic diseases. On account of examples borrowed from the literature and of our own results of studying familial forms of glaucoma, breast cancer and familial hypercholesterolemia in St. Petersburg we argue that investigations of monogenic diseases in Russia and worldwide have never been more relevant than today and that the issue as a whole deserves more attention.

In acute experiments on the mongrel anesthetized cats it was shown that following intravenous injection of catecholamines pulmonary flow always increases, meanwhile pulmonary pressure (in the most of the experiments) can be increased or decreased. After epinephrine injection the values of pulmonary pressure were varied comparing with the pulmonary flow equal increases. Norepinephrine caused the different changes both of the pulmonary pressure and flow. Angiotensin intravenous injection evoked various (elevating or lowering) changes of the pulmonary flow. In these conditions the pulmonary pressure can be increased or decreased independently from the direction of the pulmonary flow shifts. Following intravenous injection of these pressor vasoactive drugs pulmonary pressure reaches its maximal levels and returns to the initial values earlier, than pulmonary flow does. Thus we concluded that in the case of intravenous injection of pressor vasoactive drugs linear correlation is not revealed between the direction of the shifts of the pulmonary pressure and flow, their values and the time of the maximal level and duration of their changes.

Literature data analysis revealed that plasma proteins have polyfunctional action. The common property of IgG and CRP is their ability to bind to Fcy-receptors of the target cells (endotheliocytes, monocytes, macrophages, neutrophiles, lymphocytes). Moreover IgG and albumin bind to endothelial cell neonatal Fc-receptors which protect these proteins from catabolic degradation. Proteins are able to interact with each other (IgG, CRP), with cationic proteins (CRP), with acetylcholine (albumin, CRP); to possess own nuclease, peptidase, amylolytic enzyme activity and bactericidal action (IgG); to have redox properties, transport functions (albumin), pro- and antiinflammatory properties. Antiinflammatory effects of albumin are connected with its influence on cellular membrane anisotropic properties and inflammatory mediators neutralization; IgG eliminates antigens, competes with autoantibodies and allergenspecific antibodies for the binding to Fcy-receptors, has self catalytic activity and ability to enhance the antianaphylactic effects of cholinergic antagonists; CRP modulates immune cells functions and binds with decay products of disintegrated cells. Alteration in proteins production leads to disturbances in cholinergic regulation of vascular tone and several metabolic reactions and so intensifies the proinflammatory response. These data extend our notion about functions of plasma proteins and may have implications in combined application of proteins with cholinergic antagonists during inflammation.

Primary reinforcing effects are thought to be the main mechanism determining the development and maintenance of addictive behavior. Such conventional views are fully supported by significant bodies of experimental and clinical evidence on drug-seeking and taking behaviors in the studies on heroin, cocaine, ethanol, etc. However, for nicotine, the main psychoactive ingredient of tobacco, positive reinforcing effects are necessary but not sufficient for developing and maintaining addictive behaviors. The present review aimed at summarizing the key mechanisms underlying the unique abuse properties of nicotine (primary and secondary reinforcement, interaction with the reinforcing effects of other drug and non-drug stimuli, negative reinforcement, schedule-induced behavior, self-medication hypothesis, pharmacokinetics). It is also argued that understanding the contribution of all factors in nicotine dependence should facilitate optimization of the test batteries designed to detect abuse potential of novel and existing pharmacological agents.

The pathogenetic risk factors of stroke were analyzed in 3112 patients, randomized on a sex, age and type of the stroke. The various rank of risk factors, according to the type of the stroke and sex of the patients, was revealed. Index of burdening was used for the prognosis and exit of the disease. The different importance of burdening factors in different types of stroke was revealed due to gender distinctions of the patients. The postinfarction cardiosclerosis and acute infarction in males and diabetes mellitus, acute infarction and heart defects in females were detected as the most important burdening factors.

Twenty teenagers with bronchial asthma underwent immunologic examinations. The level expression of differentiation markers of lymphocyte such as CD 3⁺, CD 3⁺ CD 4^+, CD 3⁺ CD 8^+, CD 8^+, CD 3^- CD 16 & CD 56*, CD 19⁺, CD 19⁺ CD 23⁺, CD20⁺ CD 5⁺, CD 20⁺ CD 5^-, CD 3⁺ CD 25⁺, CD 4⁺ CD62 L⁺, CD 3⁺ CD4⁺CD25⁺, CD 3⁺ TC Rab^- was studied. A comparative analysis of immunological parameters showd, in teenagers with bronchial asthma versus healthy teenagers, the condition of immunity to be characterized by the changing expression of lymphocyte antigens. A lower level of CD 20⁺ CD 5⁺ and CD 19⁺ CD 62L cells, and a higher content of CD 20⁺ CD 5^- lymphocytes were observed in patients with bronchial asthma. We have investigated the content of lactoferrin and Ig E in the blood of 10 healthy persons and in that of 20 teenagers ill with bronchial asthma. Patients with bronchial asthma have the investigated indicer virtually increased. In healthy teenagers noticed significant changes of IgE and LF levels that are often higher that normal common indices allow to speak about unfavourable effect of environment on the body. An evaluation of the quantitative parameters of immunity in patients with bronchial asthma can be used in working out the immunological and prognostic criteria for the disease progression.

Objective of the study: to evaluate the early results of endovascular treatment of critical ischemia of the lower extremities (CILE) in patients with diabetes mellitus (DM).

Materials and methods: In the period between November 2004 and November 2007 transluminal ballon angioplastics (TLBAP) was performed 31 times in 30 DM patients with CILE. 20 (66.6%) patients had an ischemic ulcer on the foot, 5 (16.7%) had gangrene, and 5 (16.7%) reported ischemic pain at rest. 25 (83.3%) patients suffered from coronary heart disease, 24 (80%) had hypertension, 14 (46.7%) had cerebrovascular disease, and 8 (26.7%) patients suffered from chronic renal insufficiency. 3 (10%) patients were receiving chronic hemodialysis. The distribution of cases in terms of CILE level and type (according to TASC) was as follows: iliac type A – 1 (3.3%), femoropopliteal type A - 1 (3.3%), type B - 5 (17.2%), typе С - 12 (41.4%), type D - 11 (37.9%), calf arteries type C - 1 (4%), type D - 24 (96%). In 27 (90%) cases, the intervention was carried out on the femoropopliteal segment, in 9 (30%) cases on the tibioperoneal trunk, in 21 (70%) cases on the anterior tibial artery, in 1 (3.3%) case on the posterior tibial artery, and in 13 (43.3%) cases on the peroneal artery. Intraluminal angioplastics was performed in 70%, subintimal angioplastics in 30% of cases.

Results: TLBAP lead to the restoration of magistral blood flow up to the foot through one calf artery in 19 (63.3%) patients, through two arteries in 7 (23.3%) patients and through three arteries in 1 (3.3%) patient. In 3 (10%) cases the treatment was unsuccessful. The results of TLBAP were evaluated 3 months after the operation, a period required for the healing of ulcers. The ulcers were healed in 27 (90%) patients. These patients were categorized according to Rutherford as follows: category 1 -2 (7.4%) patients, category 2-12 (44.4%), category 3 - 8 (29.6%), categories 4 and 5-2 (7.4%) patients in each.

Conclusion: TLBAP was successfully performed in 90% of DM patients, leading to recovery from CILE in 85% of patients.

Review includes data of studies the specialized proteolytic function of human stomach in cases of tumor and non-tumor pathologies. Screened results of research inside the «pepsinogen-pepsin» system provided on biochemical and molecular-biological levels can reflect the gradual changes of physiological state and function of gastric epithelium during development of pathologic processes.

It is showed that stomach specialized enzymes, for instance, pepsinogens, can be used as markers for early diagnostics of gastric cancer pathology as well as and as perspective differential-diagnostical indicators for nontumor gastric diseases.

Various research also displayed the data about protective role of "pepsinogen-pepsin" system in supporing of physiological functioning of human organism as well as possible participation in antiinfectional and antitumor processes.

Using as basis their publications and the available literature data the authors of the editorial suggest that formation in the human organism of autoimmune complexes "modified low density lipoprotein-antibody" may have a protective character: such complexes are less atherogenic, compared to initial modified lipoproteins, and are eliminated from circulation very quickly. In the authors view the active immune response to modified lipoproteins may protect organism from premature development of atherosclerosis.