[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.

[SEVERE FORMS OF TROPICAL MALARIA: MOLECULAR GENETIC FEATURES OF THE COURSE OF THE INFECTION (REVIEW)].

The article overviews some issues of the severe course of tropical malaria. In addition to the analysis of the ongoing situation with malaria in Russia, a general clinical picture of the severe course of tropical malaria is discussed. The main part of the overview includes a detailed analysis of current data on the molecular genetic aspects of the erythrocytes' adhesion in the case of tropical malaria. The main elements involved in the process of binding red blood cells and, as a result, in the process of their adhesion to other cells of the human body were considered in detail. Data were studied and summarized not only on protein interactions between an infected red cell and its cellular environment, but also on the genetic characteristics of the parasite leading to similar molecular-biological processes. In addition to the study of protein PfEMP1 role which is nowadays well-considered in the literature, the most up-to-date but less reported data on erythrocyte adhesion proteins STEVOR and RIFIN were also included. The team of authors hopes that this publication will help to get a deeper insight into the problem of erythrocyte adhesion in the course of complicated malaria infection forms and to summarize some of the available data on this issue.

[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.

[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.

[GENETIC ASPECTS OF RESISTANCE TO MALARIA (REVIEW)].

Malaria is one of the most important and common infectious diseases in the world. The world health organization estimates 225 million malaria cases worldwide. Malaria is one of the strongest selective factors affecting the human genotype. The greatest pressure of malaria pathogens had on the inhabitants of the tropical belt, in which invasion was the main factor of genetic selection. As a result, there were genetic diseases such as sickle cell anemia, thalassemia, glucose-6-phosphate dehydrogenase deficiency and others. An important role in the pathogenesis of malaria is the stage of penetration of the parasite of malarial Plasmodium into the erythrocyte. Changes in the structure of surface antigens of red blood cells may contribute to or reduce the effectiveness of invasion. Genetic polymorphism associated with the pathogenesis and characteristics of the malaria clinic is also important in the development of malaria resistance. Understanding the genetic changes associated with red blood cell disorders and pathogenesis can provide insights into the development of new strategies for malaria treatment and prevention.

[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.

[(IMPACT OF LUNGWORM INFESTATION ON THE BIOCHEMICAL PARAMETERS OF ANIMALS DURING COMBINATION TREATMENT WITH ALBENDAZOLE AND T- AND B-ACTIVIN)].

Lungworm infection is caused by a Dictyocaulus filaria nematode parasitizing the bronchi and bronchioles of sheep and goats. Various anthelmintics, including albendazole, levamisole, fenbendazole, ivermectins, and others, are used to treat the animals. The aim of this investigation was to study the impact of lungworm infestation on the biochemical parameters of animals during combination treatment with albendazole and T- and B-activin. Experiments were carried out in 20 uninfected mongrel lambs aged 4-5 months. Infectious D.filaria larvae were given with water to 15 lambs once orally at a dose of 1000 larvae per head. 5 uninfected lambs served as a control group. The time course of changes in serum bio- chemical parameters was studied in animals. Treatment with Albena in combination with T- and B-activin in lambs ex- perimentally infested with lungworm was found to restore their biochemical reactivity. After sheep treatment with Albena alone, biochemical parameters were noted to tend to normalize, but their normal full recovery did not take place.

[Pulmonary paecilomycosis: Diagnosis and treatment].

AIM: To represent the advances of Russia and Uzbekistan in studying the problem of paecilomycosis. The goal of the investigation was to develop the diagnosis and treatment of pulmonary paecilomycosis (PP). SUBJECTS AND METHODS: Two hundred and twenty-five people, including 200 patients with bronchopulmonary infection with fungi of the Paecilomyces genus and 25 clinically healthy individuals (a control group), were examined. Clinico-anamnestic, laboratory diagnostic, mycological, and immunological studies were conducted; a lymphocyte antigen-binding test was used for differential diagnosis. Paecilomyces infection was diagnosed by microscopically examining the morphology of the fungi in the pathological material (blood, sputum) and by isolating the cultured fungi in the media (Sabouraud's and Czapek's ones). The severe complication of PP - atypical paecilomycosis-associated myocarditis (APAM) - was studied in 112 patients with helminthiasis-complicated paecilomycosis. These patients underwent using the conventional echocardiography. RESULTS: Bronchopulmonary paecilomycosis resulting from primary and secondary infection with fungi of the Paecilomyces genus was clinically manifested as chronic obstructive bronchitis (11.5%), recurrent pneumonia (13.5%), exogenous allergic alveolitis (37%), and asthma (26%) complicated by helminthiasis (12%). Iodine deficiency promotes the prevalence of paecilomycosis and echinococcosis favors Paecilomycosis infection; moreover, the helminth capsule itself serves as a nutrient medium for the development of the mycelial form of the fungus. APAM is a severe complication of PP. Almost 50% of the patients with PP presented with carditis. The patients with APAM occasionally experienced fear and the most severe intermittent pain. The latter first occurred in the chest.and irradiated to the axilla, left hand, and its fingertips, paralyzing the arm. In some patients, the pain manifested itself in both arms with abdominal irradiation, by being accompanied by faints. Current analgesics (meloxicam, tizanidine, nimesulide, morphine, promedole) in combination with fluconazole provided a temporary positive effect. CONCLUSION: Further investigations that must also include neurologists and anesthetists are required to work out effective pain relief regimens for APAM in patients with PP.

[Methodological features of DNA isolation for nested PCR for the differential diagnosis of malaria].

Current PCR assays for the differential diagnosis of malaria need to be further developed and certified in the Russian Federation. PCR may serve as a control diagnostic method. These investigations have demonstrated that an erythrocytic clot may be used as an adjunct to microscopy and the described procedure can be employed to isolate DNA for PRC in an inpatient setting.

[Procedure for Latrodectus reproduction in the laboratory setting and the preparation of the first Russian matrix from its venom to manufacture homeopathic remedies with antiparasitic activity].

The investigation was undertaken to study the biology and ecology of Latrodectus, the possibilities of its importation to Russia from other countries, to breed Latrodectus in the laboratory setting, and to design the first homeopathic matrix of Latrodectus to manufacture homeopathic remedies. The authors were the first to devise a method for Latrodectus breeding in the laboratory setting of Moscow and its vicinities. The Latrodectus bred in the laboratory is suitable to manufacture drugs and in captivity they do not lose its biological activity. The authors were the first to prepare a homeopathic Latrodectus matrix for homeopathic medicines, by using the new Russian extragent petroleum. Chromatography mass spectrometry was used to identify more than a hundred chemical compounds in the Russian petroleum. The biological activity of the petroleum Latrodectus matrix for the manufacture of homeopathic remedies was highly competitive with that of the traditional Latrodectus venom matrix made using ethyl alcohol. The homeopathic Latrodectus matrix made using glycerol lost its biological activity because of glycerol. The biological activity of homeopathic matrixes made from Latrodectus inhabiting the USA, Uzbekistan, and the south of Russia and from that bred in the laboratory was studied. The homeopathic matrix made from the Latrodectus living in the Samarkand Region, Republic of Uzbekistan, has the highest biological activity.

[The agent Latrodectus and canine paecilomycotic eclampsia as a laboratory model in the survey of treatment for mycoses and parasitic diseases].

The extragent used to prepare a Latrodectus mactans hydrocarbon extract is a multicomponent system composed of alkanes, alkenes, and arenes. More than 100 compounds were identified in the hydrocarbon extract (petroleum). The petroleum matrix of Latrodectus mactans was first obtained to manufacture homeopathic remedies. The authors could prepare the first Russian homeopathic medicine from Latrodectus mactans, which proved to be effective in treating canine eclampsia. Canine experiments provide a rationale for the authors' choice as the only homeopathic remedy among thousand known drugs to treat female eclampsia. It is Latrodectus mactans that is in the list of homeopathic medicines permitted for use in accordance with Order No. 335 (Supplement 2) of the Ministry of Health and Medical Industry of Russia, issued on November 29, 1995. It is manufactured from Latrodectus mactans living in the USA.

[Development of a new hydrocarbon extract from the medicinal raw material of Circassian walnut (Juglans regia) and study of its antiparasitic activity].

The authors developed a technology for preparing a hydrocarbon extract from the medicinal raw material of Circassian walnut (Juglans regia), including its green fruits, green leaves, and fresh roots. To prepare the preparation, they obtained for the first time a new extragent called petroleum Russia that was found to contain more than hundred chemical compounds by chromatography mass spectrometry. The new agent was named irillen. Experiments on albino mice and albino rats established that the new agent was low toxic. The lethal doses of irillen were calculated: LD50 was 16377 +/- 457.5 mg/kg; LD16 = 12986.4 mg/kg; LD84 was 18976.6 mg/kg for albino mice; LD50 was 16998.0 +/- 535.4 mg/kg; LD16 = 12875.3 mg/ kg; LD84 = 18583.4 mg/kg for albino rats. The irillen prepared by the authors should be referred to as a low toxic and practically nontoxic agent (Toxicity Class IV and V). Irillen has a broad spectrum of antiparasitic activity. It is effective in treating toxocariasis in dogs, larval alveolar echinococcosis, ascaridiasis, and eimeriasis in chickens, and siphachiasis.

[Immunorehabilitation in patients with paecilomycosis-complicated echinococcosis and asthma].

Paecilomycosis is a new type of systemic mycosis caused by different species of fungi of the genus Paecilomyces. Paecilomycosis-complicated echinococcosis and asthma run a severe course. A complication of mycosis is accompanied by secondary immunodeficiency. A good result was obtained in the treatment of ill children by using the fungicide diflucan and the immunomodulator polyoxidonium. In the examinees with paecilomycosis-complicated echinococcosis, secondary immunodeficiency was characterized by a statistical significant reduction in the blood levels of the lymphoid cells CD3+, CD4+, CD8+, CD16+, CD21+, by phagocytosis, a decrease in its quantitative parameters, and an increase in the counts of immunoglobulins and circulating immunocomplexes. To normalize the immune status in patients with paecilomycosis-complicated echinococcosis, it is expedient to postsurgicallyuse fungicides, such as nizoral, diflucan, orungal, mycosyst, and the immunomodulators polyoxidonium and irillen.

[Transformation of the fungus Paecilomyces variotii and the causes of host cell lysis at the boundary with a fungal mycelium-containing Echinococcus capsule].

Experiments were carried out on animal species. The experiments used 30-day chicks, 80 rats, and 70 rabbits. Three hundred and twenty-nine patients with echinococcus complicated by paecilomycosis were meticulously examined. The fungi of the genus Paecilomyces undergo two transformation directions: the saprotrophic mycelial form of the fungus Paecilomyces variotii transforms to the tissue parasitic one as a globular form of spherules that transforms to the mycelial form in larval Echinococcus infection because the cyst capsule is a favorable environment for growth of fungal mycelia. The growth and aggressiveness of larval Echinococcus in the human lung are associated with the fact that fungal mycelial fibrous tunic contains Paecilomyces that have been first used to isolate active hyaluronidase that lyses host cells. Pulmonary echinococcosis complicated by the tissue form of paecilomycosis can be complicated by the mycelial form of the fungus of the genus Paecilomyces, by afflicting the nails and skin of patients, which requires particular treatment after surgery for hydatid disease. The chicks that had been brooded in an incubator and grown under special conditions to rule out fungal infection were first contaminated with the fungal mycelium labeled with methionine, sodium sulfate, sodium phosphate, or iodine. Each chick received 0.5 g of the labeled fungal mycelium. Regardless of the contamination mode, all the chicks from 3 groups were infected with Paecilomyces; the spherules exhibited labeled isotopes. Thus, it has been first conclusively proven that the diagnosis of paecilomycosis based on the blood detection of fungal globular spherules is valid and easy-to-use in any health care facility.

[Amino acid exchange in paeci lomycosis-complicated echinococcosis].

The authors have detected atypical paecilomycosis-associated myocarditis with impaired amino acid exchange and pain syndrome for the first time. At first, pain occurs in the chest and radiates into the axilla, to the left arm to the finger tips, by paralyzing the arm. In some patients, pain manifests itself in both arms with radiation to the belly, by accompanying by fainting. The skin is wet, cold; the pulse is frequent and of poor volume and difficult-to-count. Heart pain spreads into the armpit and down the arm, by making the fingers numb. Attempts to use current analgesics (movalis, sirdalud, nimesil, morphine) in combination with fungicides (diflucan, mycosist, orungal) have failed to yield positive results. The homeopathic drug Latrodectus mactans, prepared from caracurt venom, in combination with the authors' designed diet and other homeopathic agents have relieved pain syndrome and normalized amino acid exchange, which offered possibilities for successful surgical treatment for echinococcosis with later recovery.

[Experimental rationale for a procedure for correction of the residual cavity in hydatidectomy].

Thirty-six piglets (15 days old) were inoculated with Echinococcus according to the authors' procedure. Hepatic hydatid cyst growth in the piglets was ultrasonographically monitored 3 months after inoculation. In 15 piglets, the size of hepatic hydatid cysts was as high as 6.5 x 8.5 cm 5 months after infection. The cavity of larvocystic fibrous capsule was eliminated, by inverting the resection margins inward with interrupted catgut sutures. For content aspiration, the cystic bed was occasionally drained by a polyvinyl chloride tube with two side holes, which was brought outward through an individual incision. Thesubhepatic area was also drained by a "cigar" tampon through an individual incision. The wound healed in layers, tightly. Marginal resection of the liver was performed to stimulate regenerative processes in the resected area.

[Echinococcosis complicated by paecilomycosis].

Two hundred and thirty-six echinococcosis patients aged 17 to 70 years were examined for paecilomycosis. Seventy-five subjects of different ages who were considered to be clinically healthy were prepared as a control. Of them who had physiological parameters of blood fungi, 24 subjects, including 9 subjects aged 17 to 23 years and 15 subjects aged 15 to 30 years, were eligible. The other examinees were patients with paecilomycosis of varying stages. Nizoral, fluconazole, diflucan, orungal, mycosyst, and teknazol, which have been tested by the authors, are proposed for use in paecilomycosis-complicated echinococcosis prior to and after surgery. It is advisable to use one fungicide. In this respect, the authors have conducted clinical trials that have yielded positive results.