[PHARMACOGENETIC ASPECTS OF TREATMENT OF PATIENTS WITH CHRONIC HEART FAILURE (REVIEW)].

This article reviews data for pharmacogenetics findings for treatment for chronic heart insufficiency of heart failure. Also, it discusses connections of genetic polymorphism with a risk of developing heart failure and how it affects the choice of a treatments medicine. The article investigates genetically determined factors of the risk of developing glycoside toxicity. One of the causes is polymorphism of the MDR1 gene encoding glycoprotein P, a transporter, that is involved in the absorption of drugs in the intestines and excretion by the kidneys. Also, the genetic characteristics of ACE in patients with heart failure are discussed. The data is presented from the study of the role of genetic liver metabolism polymorphism regarding efficacy and safety of loop diuretic torasemide. Data for genetic polymorphism of the metabolism of the main beta blocker, used in chronic heart failure metoprolosuccinate is also discussed. Data for roll ß1-AP polymorphism in the clinical use of ß-AB in patients with heart failure. Further observations are needed from longer studies, that will evaluate long-term efficacy and safety outcomes for medicines related to genetic traits.

[CLINICAL DIAGNOSTIC VALUE OF OXIDATIVE STRESS MARKERS IN PATIENTS WITH CHRONIC HEART FAILURE. OPPORTUNITIES OF THEIR PHARMACOLOGICAL CORRECTION BY ETOXIDOL].

Purpose - to evaluate the effectiveness of a fundamentally new antioxidant drug Amoxidal malate in patients with chronic heart failure (CHF) and its effect on marker of oxidative stress 2,3-diphosphoglycerate -2,3-DPG regulating the dissociation of oxyhemoglobin into hemoglobin and oxygen depending on the partial pressure of oxygen in the lungs and effect on other markers of oxidative stress. Clinical study of etoxazole was conducted in the city hospital N 23. 32 people were examined. At the age of 55 to 76 years (men and women) with coronary heart disease, stable angina, who had a myocardial infarction with a diagnosis of chronic heart failure II-IU FC according to the NYHA classification. Hypertension was diagnosed in 15 patients and type 2 diabetes mellitus in 8 patients. The study included patients with an ejection fraction of less than 40%. Permanent atrial fibrillation was diagnosed in 6 patients. Patients were divided into 2 groups: 1 main group, 22 patients who were added to the standard therapy with intravenous infusions of Ethylmethylhydroxypyridine malate, 2 group - control group, 10 people who received standard pharmacotherapy of CHF. Indicators of oxidative status, especially 2,3-DPH, were evaluated. and also, the voltage of oxygen (pO2), pCO2, pH, concentration of superoxide dismutase (SOD), malondialdehyde (MDA), the concentration of total peroxides in the blood of these patients. Etilmetilgidroksipiridinamaalat restores oxygenation of the blood in patients who are intravenously introduced Amoxidal compared with patients not receiving this treatment with CHF IV FK. Analysis comparative assessment of treatment results shows that the addition of Ethoxide to standard therapy is most beneficial effect on patients> IU F. K. the Inclusion of the new Patriotic antioxidant drug Amoxidal in standard therapy of patients with CHF is pathogenetically justified and promising.

[CLINICAL CASE: THE SIDE EFFECTS OF STATINS].

The clinical studies, conducted in recent years, suggest that statins increase the activity of telomerase and by that decelerate speed of telomerase shortening. Thus, on one hand, it reduces a risk of cardiovascular diseases development, decelerate aging, but on the other hand, increasing the activity of telomerase, lead to expression rising of gene hTERT, that can make prerequisites for malignancy. That's why, it's necessary to study the subject and develop reliable criteria for safety use of activators-telomerase.

[PECULIARITIES OF INTERACTION IN THE "PARASITE-HOST" SYSTEM IN HIV-INFECTED PATIENTS WITH TOXOPLASMOSIS: LITERATURE AND CLINICAL CASE REVIEW].

The article presents a review of current literature data on the development of opportunistic toxoplasmosis in patients suffering from HIV infection and a clinical case of an immunocompromised patient with toxoplasmosis. Current information concerning the incidence of toxoplasmosis in Russia and other countries are presented. Special attention is paid to the Toxoplasma gondii interactions with the host cell in HIV-infected people. The mechanism of parasite penetration into the host cell and subsequent modifications that the parasite makes with the occupied cell are analyzed in detail. The significance of the chosen topic is illustrated by the description of a clinical case of toxoplasmosis in an HIV-infected patient. The authors hope that the article will help to attract attention of the professional community to the problem of opportunistic infections in HIV/AIDS carriers, and in particular to the mechanisms of the "parasite-host" interactions in patients with toxoplasmosis.

[THE SIGNIFICANCE OF THE SYSTEM APPROACH IN THE STUDY OF THE GENERAL ADAPTATION SYNDROME' REACTIONS].

The article discusses the problems of the process of environmental adaptations appearance which are based on the general principles of functional systems' constitution. The value of the theory of functional systems development as the basis for physiological cybernetics (P. Anokhin, 1935) is also given. A general adaptation syndrome ("a stress - syndrome") that was discovered by H. Selye is chosen as an example to explain the development of the stages of the functional system of the stress, the sequence and value of ongoing physiological reactions and negative feedback interactions. The stress - syndrome reactions are the nonspecific response of a particular organism to various factors: emotional shock, trauma, infections, surgery, burns etc. The article also paid attention to the reasons and conditions for the failure of adaptations' emergence and the transformation of adaptive reactions into pathological ones. The key role of stress syndrome reactions as the main or auxiliary etiological factor in the development of coronary heart disease, hypertension, atherosclerosis, lesions of the stomach and duodenum, immunodeficiencies, etc. is indicated. To be effective in interactions with the environment, organisms have developed different mechanisms which are not only activating but also suppressing the excessive activity of the functional stress system that damages the organs. Therefore, the article considers the significance of negative feedback adaptations that act as stress - initiating and stress - limiting mechanisms.

[COMPARATIVE EFFICACY OF DOXYCYCLINE AND GLUCANTIME IN THE TREATMENT OF LEISHMANIASIS IN VITRO].

In this study, we studied the activity of the antibacterial drugDoxycycline (Russia), and the control was the drug of pentavalent antimony - Glucantim (France), which for a long time was the "gold standard" in the treatment of any form of leishmaniasis. In the course of the experiment, the leading positions of doxycycline established in vitro. Its minimum doses lead to absolute suppression of the mobility of the pathogen L. major. Increasing the therapeutic dose of the drug is not justified. Comparison of this drug with the gold standard of therapy with meglumine antimonate (glucantim) showed its superiority in all indicators.

[STRUCTURAL, MOLECULAR AND FUNCTIONAL FEATURES OF THE TREMATODE TEGUMENT AND OF ANTHELMINTIC DRUGS DEVELOPMENT (REVIEW)].

Helminth infestations, including trematodoses, are a group of the most common diseases in the world. Trematodoses cause significant damage to human health, lead to various complications, which also causes significant economic damage. To develop effective anthelmintic drugs, it is necessary to study the structure and physiology of parasites and interaction with the host body. To create specific anthelmintic drugs, it is necessary to study the features of biochemistry and molecular biology of the structural components of the covers of trematodes. The is important role of the tegument in the evasion of the immune response. The trematode tegument antigens are good candidates for the development of anthelmintic vaccines. It is important to study the trematode genome and identify specific enzyme systems. Proteases of tegument of trematodes are digestive enzymes that can destroy the immunoglobulins of the host to modulate the immune response. Identification of specific differences in protein and enzyme systems will create more effective drugs for the treatment of helminthiasis.

[COMPARISON OF THE EFFECTIVENESS OF DRUGS FOR THE TREATMENT OF CUTANEOUS LEISHMANIASIS IN VITRO].

In this study, we studied the activity of three antibacterial drugs: Cefotaxime (Claforan, France), Ceftriaxone (Russia) and Doxycycline (Russia). The control group is a pentavalent antimony drug - Glucantim (France), which has been the "gold standard" for a long time in the treatment of any form of leishmaniasis. During the experiments, the leading positions of doxycycline and ceftriaxone established in vitro. Minimal doses of both drugs lead to absolute suppression of the mobility of the pathogen L. major. Increasing the therapeutic dose of drugs is not justified. Comparison of these drugs with the gold standard of therapy with meglumine antimonate (glucantim) showed their superiority in all indicators.

[STRUCTURAL, MOLECULAR AND FUNCTIONAL FEATURES OF NEMATODE SURFACES AND THE POSSIBILITY OF ANTHELMINTIC DRUGS DEVELOPMENT (REVIEW)].

Helminthiases caused by parasitic nematodes are widespread in different regions of the world. The main adaptation for overcoming adverse conditions is a barrier properties of the cuticle surface structure, which differs from the membrane teguments of trematodes and cestodes. Different types of nematodes have specific structural and biochemical adaptations at different stages of their life cycle. While creating specific areas of habitat and nutrition, some types of parasites change the morphology and functioning of the host tissues. Ascaris suum and Caenorabditis elegans were widely used as model organisms in the study of genetics, biochemistry of nematodes. Studying of biochemistry and molecular biology of structural components of nematode surfaces is important for development of effective and safe anthelmintic drugs. The differences in the structure and functioning of transport enzymes of parasites and humans will help to create effective specific inhibitors and anthelmintic remedies. An important point of application of anthelmintic drugs can serve as inorganic ions transport proteins in the membranes of the surfaces. Glycolipids of cuticle contribute to the evasion from the host immune system, protecting the surface proteins from degradation by proteases. Study of helminth surfaces makes an important contribution to the development of anthelmintic drugs and vaccines, for helminthiasis treat.

[CHARACTERISTICS OF PARASITIC PROTOZOA METABOLISM AND POSSIBILITIES OF ANTIPROTOZOA DRUG DEVELOPMENT (REVIEW)].

One of the most poorly studied areas of protozoology is metabolic processes of parasitic protozoa. Study of the biochemistry of parasites required for the development of effective chemotherapy of protozoal diseases. Some amitochondrial parasites of humans, such as Giardia intestinalis, Entamoeba histolytica, Trichomonas sp., living in an environment with low oxygen content, have specialized cellular organelles-hydrogenosomes (like mitochondria provide cells with simple energy). The study of the functioning of these organelles allows us to consider them as targets for the development of аntiprotozoal drugs. The target for chemotherapy in the treatment of trypanosomiasis can be processes related to the characteristics of the glycolytic pathway or a decrease in the level of energy substrate, such as glucose. This leads to a rapid decrease in ATP levels in the cell of the parasite, an overall loss of mobility and disappearance of trypanosomes from the bloodstream of the infected host. Also, glucose transporters located in the membrane of the parasite can be targets for drugs.

[The pathomorphological changes in the kidneys of white mice with experimental trichocephaliasis and after the use of anthelmintic preparations]. / Patomorfologicheskie izmeneniia v pochkakh belykh myshei pri éksperimental'nom trikhotsefaleze i posle primeneniia antigel'mintnykh preparatov.

The experiments were carried out with 170 white mice divided into 4 groups. The first group consisted on 72 intact animals, administered subcutaneous ivomek (0.01 ml/kg) and oxfendasole (10 mg/kg) per os; Group 2 consisted of 15 animals with induced trichocephaliasis, administered no anthelmintics. The third group, 72 animals, were infected with Trichocephalus muris invasion eggs and administered anthelminthic agents on day 46 postinfection. The fourth group consisted of 11 intact animals, neither infected, nor treated (reference group). The animals were decapitated 3, 12, 24 and 72 h after the drug administration and histologic examination of the kidneys was carried out. The findings evidence that the morphologic changes in the kidneys of mice with trichocephaliasis are characterized by alternating proliferative processes. Both the drugs used were found characterized by a more or less pronounced nephrotoxicity. Ivomek induced the most marked structural changes in the kidneys of intact animals. The changes in the kidneys of intact mice were more manifest after the drugs administration than in intact animals.

[A morphological and histochemical study of the large intestine of white mice with experimental trichocephaliasis and after the action of some anthelmintic preparations]. / Morfologicheskoe i gistokhimicheskoe issledovanie tolstoi kishki belykh myshei pri éksperimental'nom trikhotsefaleze i posle vozdeistviia nekotorykh antigel'mintnykh preparatov.

Administration of levamisole, oxphendasole in dose 10 mg/kg and especially of ivomeck in dose 0.01 ml/kg of body weight damages the large intestine mucosa of intact mice and of mice with experimental T. muris infection. Epithelial cells dystrophy, the goblet cells destruction and the diffuse leucocytes infiltration of the intestinal wall, maximal 12 hours after the drugs administration, were most marked in animals treated with ivomeck. Pathomorphological changes in the gut mucosa after the drug administration to infected animals were significantly higher than in intact ones. That permits to conclude that the damage of the intestinal wall is due to the toxicity of the drugs, and perhaps with the damage of mucosa by the nonspecific (allergic) response to the chemotherapy.