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The research involves 481 (61,3%) male and 303 (38,7%) female pupils in the hygienic assessment of daily consumption of micronutrients by the children and teenagers that live in rural areas of the Fergana region. The research assesses the conformity of the diet of pupils with the San NandR 0007-2020 requirements of “The average daily diet norms for providing a healthy diet for age, gender and professional groups of the population of the Republic of Uzbekistan”. During winter-spring and summer-autumn seasons, pupil’s consumption degree of bakery products tends to be 133,7-115,6%, their consumption of mung bean, phaseolus, and cicer of legume products is 2,3 times less in the winter-spring season and 2,1 times less in the summer-autumn season, and their consumption of rice and porridge is 56,6-43,3% in relation with the norm. Moreover, there are not enough fish, dairy, and meat products in their diet. However, sugar, confectionery, and margarine exceed the norm 1,7 times in the winter-spring season and 1,3 times in the summer-autumn season. In the consumption of micronutrients, retinol reaches 79,8-93,8% and 81,1-91,8%, tocopherol reaches 63,8-73,5%, and other vitamins also don’t conform with the physiologic norm and hypovitaminosis causes difficulties in pupils’ growth and development.

Paecilomyces variotii is a commonly occurring species in air and food, and it is also associated with many types of human infections. Tissue forms of the fungus Paecilomyces variotii or their cytoskeletons were revealed in the cytoplasm of erythrocytes in patients with allergy and bronchial asthma in paecilomycosis. Our study was aimed at investigating the role of red blood cells in the mechanisms of the nonspecific protection of the host in conditions of chronic persistent infection of the blood with the fungus of the genus Paecilomyces. We examined a total of eighty-four 16-to-72-year-old patients (39 men and 45 women) presenting with activation of paecilomyces infection in blood. We used laboratory, biochemical, allergic-and-immunological and microbiological methods of study. Fungal cultures were identified phenotypically and by means of phylogenetic analysis.Our findings are suggestive of a new type of the oxygen-dependent mechanism of cytotoxicity of erythrocytes, which is caused by permanent formation of reactive oxygen species as a result of non-enzymatic oxidation of haemoglobin to methaemoglobin. The resulting superoxide anion radical (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH-) exhibit a powerful bactericidal action which is, probably, activated when the fungal cells are captured and immersed in the erythrocyte cytoplasm or in a closed cavity formed by RBCs around large fungal cells. In conditions of chronic blood infection with tissue forms of fungi of the genus Paecilomyces oxygen-dependent cytotoxicity of erythrocytes is the main mechanism of readjustment of blood from the infectious agent of Paecilomycosis.

A 49 year old woman with signs of chronic sepsis, hepatomegaly, and high eosinophil count was under long-term examination including consultations with an oncologist, parasitologist, and hematologist, diagnostic laparotomy, and studies of liver biopsies. Seeding blood samples onto Saburo’s medium resulted in the growth of Paecilomyces variotii Bainier colonies. Counting mature spherules of the fungus revealed 59000 spherules per 1 mcl compared with the normal value of 1000-6000 which suggested paecilomycotic etiology of sepsis. The histological study of liver biopsies demonstrated hemorrhagic foci and eosinophilic infiltrates around fungal spherules. The clinical recovery of the patient was achieved after 3 courses of pulsed terbinafine therapy (500 mg/d every other day for 14 days during a month) in combination with vitamins and i/v infusion of 100 ml of a fluconazole solution (2 mg/ml) every third day (10 procedures during a course of therapy).

We studied the influence of activation ofpecilomycotic infection in blood on the morphofunctional state of myocardium based on the clinical and pathomorphological data. The study included 23 patients with bronchial asthma (BA) concomitant with pecilomycosis after acute viral respiratory infection; protocols of autopsies and pathological sections of the heart muscle of the patients who died from asphixy and acute cardiac insufficiency were analyzed. Histological sections showed up vascular dystonia of the microcirculation bed, arteriole spasms, wall destruction in small and medium-size vessels and the adjacent muscular tissue, stromal oedema, valvular swelling, andperiwall endocarditis. Cardiac cavities and coronary vessels contained erythrocyte-rich thrombi with ferulas of Paecilomyces at different stages of development. Clinical manifestations of destructive changes in the heart muscle developing under effect of Paecilomyces infection had the form of rhythm and conductivity disorders. The local protective inflammatory reaction of productive type had the form of intermediate and vascular-type myocarditis passing to postmyocarditic cardiosclerosis. Periodic bursts of activation ofpecilomycotic infection in blood with the accumulation of fungal phospholipase A2 and lipid metabolites produced membranotoxic effect and can play the key role in the development of atherosclerosis and hypertensive disease in patients with BA and pecilomycosis.

The actuality of the problem is is conditioned by detection of infection of patients' blood with fungi genus paecilomyces in the form of carriage or activation of pecilomycosis infection with clinical manifestation of allergic diseases and bronchial asthma. The purpose of study is to analyze clinical and immunologic characteristics of bronchial asthma under pecilomycosis and to develop new approaches to its laboratory diagnostic in conditions of the primary health care unit. The complex examination of patients that included collection of allergy anamnesis, physical examination, application of laboratory, cytology, immunology and microbiology analysis was carried out. The diagnosis of pecilomycosis was established at the basis of express-diagnostic using direct count of mature spherules and yeast-like cells of fungi genus Paecilomyces in blood sample, detection of specific IgE- and IgG antibodies to allergen of fungus Paecilomyces spp. in blood of patients and cultural analysis. The clinical immunological characteristics of atopic and endogenous (non-atopic) forms of bronchial asthma in 143 patients were examined. The activation of pecilomycosis was established in 120 (83.9%) patients: the content of mature spherules of fungus genus Paecilomyces in blood varied from 8 000 to 55 000 (in average 17 500±755) in 1 mkl at the standard 1000-6000 (in average 3417±433) in 1 mkl. The specific IgE- and IgG antibodies to allergen of fungus Paecilomyces spр. were detected (57% and 81% correspondingly). The development of bronchial asthma is induced by activation of pecilomycosis in blood: it occurred against the background of acute respiratory viral infection in 74 patients (62%), seasonal and age fluctuations of immune status in 34 patients (28%), under stress impact in 12 patients (10%). The immune response to infection with fungus genus Paecilomyces is conditioned by mechanisms of non-specific resistance and specific immunity. The eosinophils and natural killers are involved into sanation of blood from fungal cells of non-phagocyting sizes using antibodies-mediators of specific IgE and IgG antibodies to allergen of fungus Paecilomyces as effector cells in reaction of antibody-dpendent and cell mediated cytotoxicity. The phagocytosis of small fungal forms was detected: endospores by monocytes, neutrophils, eosinophils and cytolysis of fungal cells by erythrocytes. The obtained data permits to differentiate carriage or activation of pecilomycosis in blood of patients with bronchial asthma, to mark out individuals with atopic or non-atopic profile of immune reaction determining specificity of their immune defense from agent of fungal infection and clinical picture of disease. The algorithm is proposed concerning diagnostic of bronchial asthma of pecilomycosis etiology in conditions of primary health care unit.

The fungi genus Paecilomyces are spread everywhere in nature. They attract attention from the middle of 1960s as a cause of development of septic endocarditis, sepsis, pneumonia and other types of pathology developed against the background of immunodeficiency. They induce development of infectious allergic alveolitis and bronchial asthma. The cultural features and pathogenic characteristics of clinical isolates (n=6) of fungus Paecilomyces variotii Bainier (1907) are studied. All isolates are separated from blood of patients with bronchial asthma visited allergologist of Moscow polyclinic. The culture of cells of embryonic kidney of bull-calf morphology and biological characteristics of tissue parasitic forms of fungus were analyzed. The typical sign of parasitic form of fungus P. variotii Bainier (1907) was a development of chlamydospores containing globe-shaped formations - endospores. The analysis of transformation of mycelial saprophyte form of fungus into tissue parasitic form established involvement of chlamydospores and apparently others organs of fruiting of vegetative body of fungus into transition to parasitic way of life in host organism with development of spherules and yeast-like cells. The cycle of development of tissue parasitic form from endospore to mature tissue form comprised 6 hours.

As gastroesophageal reflux disease is a "disease of the XXI century", the relevance of its diagnosis at early stages is high. Using transnasal fibroesophagogastroduodenoscopy, which is significantly better tolerated by patients, and the technology of intelligent color coding of pathology of the mucous membrane FICE, can diagnose the earliest manifestations of GERD in the form of inflammatory noerosive changes in the mucous membrane of the distal esophagus, to evaluate the failure of the lower esophageal sphincter; to make a prognosis for the disease, and to formulate a rational policy of conducting the patient.

The lipolytic activity of extract of mycelium and cultural fluid of fungus Paecilomyces viridis and their protein fraction was investigated. The micelium of fungus Paecilomyces viridis is a weak producent of exogenic phospholipase A2, possessing the hemolytic activity. The optimum of zungal phospholipase A2 activity was within a range of pH 8.5-9.0 which coincides with the optimum of activity of phospholipase A2 from venoms of snakes and insects.

The fungus Paecilomyces variotii is known to develop as a saprotrophic mycelial form in the soil. When penetrating into the human organism or placing into a medium containing cultured cells it transforms into a parasitic flesh form. This form of the fungus was shown to undergo 3 morphological stages: endospore, juvenile (intermediate) form and mature sphaerula. The transformation of the mycelial form into parasitic one occurs in the biological media containing cells of the host, inside or outside the cell. The morphological structure of mycelium of P. variotii developed from the flesh parasitic form is different in aerobic and anaerobic conditions. In the former case, the spore production takes place by means of phialides, and in the latter case it occurs inside the mycelium.

Preincubation of blood, sputum, breast milk, and feces samples from patients in heparin-treated medium 199 for 18-24 h at ambient temperature to preserve viability of Paecilomyces tissue form when transferring the fungi from host to ambient temperature regimen results in transformation of the fungi into mycelium form in favorable conditions, which fact permits elevating the isolation rate of this fungus from 1.5 to 44-73 percent.

Primary or secondary infection of the lungs with fungi of the Paecilomyces family (P. variotii and P. viridis) gives rise to the development of infectious allergic bronchopulmonary paecilomycosis characterized by the presence of chronic allergic interstitial pneumonia and obstructive bronchitis, bronchial asthma, total and pulmonary eosinophilia, the presence of the tissue parasitic form of the fungus in sputum, blood, pulmonary tissue, the presence of allergen-specific IgE and/or IgG antibodies in patients' sera, immediate or double (20 min and 6 h) reaction of the skin to administration of allergen of Paecilomyces, by not infrequent combination of lung damage and impairment of other organs as well as by chronic relapses.

The clinical and experimental studies showed that etiology and pathogenesis of allergic alveolitis in the inhabitants of the Samarkand Region stem from mycosepsis caused by Paecilomyces variotii Bainier, that is immunocomplex affection of the small and middle vessels and cell-mediated granulomatous inflammation of the tissues.

Among patients of an allergological center there appeared cases of respiratory and cutaneous allergy provoked by fungal infection Paecilomyces varioti Bainier. In the soil the fungi occurred in the mycelial form while in humans and animals the infection manifested in a parasitic hemotropic-tissue form. Pathogenesis of the disease is related to chronic sepsis-like state produced by the persistence of parasitizing hemotropic-tissue Chlamydiaceae-like fungi in blood and tissue cells, sensitization to them, impairments of small and medium size vessels by immunocomplex type, and delayed hypersensitivity in tissues.