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We studied the effect of laser radiation of moderate intensity with a wavelength of 970 nm on the efficiency of colony formation of rat bone marrow mesenchymal stem cells (MSC) in vitro. In this case, photobimodulation and thermal heating of MSC occur simultaneously. This combined laser treatment allows increasing the number of colonies by 6 times in comparison with the control and by more than 3 times in comparison with thermal heating alone. The mechanism of such an increase is associated with combined thermal and light effects of laser radiation of moderate intensity, which stimulates cell proliferation. This phenomenon can be used as the basis for solving the most important task of cell transplantation, associated with the expansion of autologous stem cells and activation of their proliferative potential., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the formation of the reparative regenerate of the skin wound in rats under the effect of drug products based on keratan and secretome of bone marrow mesenchymal stem cells (MSC), as well as bone marrow cells (native and exposed to laser radiation with a wavelength of 1.56 μm). Due to the biological affinity for the dermal tissue, keratan preparations being applied to the skin stimulate regeneration of the wound defect. This substance in the form of a gel is characterized by high diffusion capacity, penetrates into the deeper layers of the dermis, and promotes the growth of the granulation tissue. Application of an ointment prepared on the basis of MSC secretome promotes quick transition of the healing process from the inflammatory to the regenerative stage. Thus, bone marrow cells were successfully used for skin wound healing. The results of the use of bone marrow cells for the healing of skin wounds were successful; bone marrow exposed to laser radiation demonstrated high efficiency in promoting reparative processes.

We studied the effect of non-thermal argon plasma on proliferative activity of bone marrow multipotent stromal cells in vitro. Treatment of stromal cell suspension with pure argon did not affect their proliferation. The cells treated with non-thermal argon plasma and explanted in the treatment medium demonstrated growth inhibition by 30-40% in comparison with the control. Multipotent stromal cells treated with plasma and after centrifugation explanted in normal medium within 12 min demonstrated accelerated growth. The total cell growth from the pellet and supernatant significantly exceeded the control values. We also analyzed adhesion and proliferative activity of multipotent stromal cells treated with non-thermal plasma on bioresorbable carriers. The cells adhered and proliferated on all types of studied samples. Adhesion properties of scaffolds differed. Caprolactone was found to be the most suitable material for adhesion and proliferation of multipotent stromal cells.

We created an anisotropic material based on collagen sponge and reactive polylactide structured by laser photopolymerization. The combination of collagen with reactive polylactide improves the resistance of the formed matrices to biodegradation in comparison with collagen sponge, while the existence of sites with different mechanical characteristics and cell affinity on the matrix provides directed cell growth during their culturing. It was shown that reinforcement of the collagen sponges 7-fold increased the mean Young's modulus for the hybrid matrix without affecting its cytotoxicity. The developed matrix provides cell adhesion and proliferation along reinforcement lines and can be used for fabrication of tissue engineering constructs.

We studied the possibility of restoring the integrity of the Achilles tendon in rabbits using autologous multipotent stromal cells. Collagen or gelatin sponges populated with cells were placed in a resorbable Vicryl mesh tube and this tissue-engineered construct was introduced into a defect of the middle part of the Achilles tendon. In 4 months, histological analysis showed complete regeneration of the tendon with the formation of parallel collagen fibers, spindle-shaped tenocytes, and newly formed vessels.

Oropharyngeal candidiasis in 512 HIV-infected patients at the late stages of the disease was studied with special reference to the clinical and microbiological characteristics of this condition. The diagnosis was established based on the results of the clinical and microbiological examination of the patients including investigation of the tissue samples taken from the oral cavity and the throat with the use of the device specially developed for this purpose. It was shown that the disease existed in various clinical forms the most common of which were monocomponent pathology represented by pseudomembranous candidiasis in 37.5±2.14% of the patients, the two-component mixed form (pseudomembranous candidiasis with concomitant angular chelitis) diagnosed in 27.5±1.97% cases, and the ternary form (the combination of pseudomembranous candidiasis, acute atrophic process, and angular chelitis) documented in 11.9±1.43% patients. The main clinical features of the disease included the combination of its various forms, multiple localization of the pathological process, and its polymorphous manifestations. Changes in the clinical course of oropharyngeal candidiasis associated with the progression of HIV from the 4A to the 4B stage were detected for the first time. They were shown to be accompanied by variations in the species composition and concentration of fungal flora in the crypts of the palatine tonsils and its sensitivity to fluconazole therapy.

Aim: Comparative assessment of the efficiency of application of different therapeutic schemes for post-contact prevention (PCP) of HIV infection in health providers., Methods: Medical personnel that had professional contacts with HIV-infected patients (n=44) were given medications for PCP. 19 of them (group 1) used phosphazide, 25 (group 2) combivir (lamivudine + zidovudine) in combination with kaletra for 4 weeks after the contact. Phosphazide (AZT Farma K.B., Russia) was used at a dose of 0.4 g twice daily, other medications in standard doses. The results were evaluated 4 weeks, 3, 6, and 12 months after PCP from the safety of the treatment and the absence of professional HIV infection., Results: The medical personnel showed no signs of HIV infection throughout the entire period of observation. The safety of therapy was confirmed by the absence of myelohepatotoxic effect of the preparations. Combivir therapy caused a 1.8-fold rise in AST activity of within 4 weeks after onset of PCP (p<0,05). Phosphazide produced no such effect., Conclusion: The above results indicate that both schemes ofantiretroviral activity are 100% efficient as PCP of HIV infection, but phosphazide has an advantage of higher safety and better tolerability.

We studied the effects of physical factors (acoustic impulses of laser-induced hydrodynamics, AILIH, and EHF-radiation) on the formation of heterotopic bone marrow organs. Suspension of precipitated mouse bone marrow cells was exposed to AILIH and EHF or their combinations (AILIH+EHF, EHF+AILIH). The developed tissue engineering constructions (gelatin sponges containing 107 nucleated bone marrow cells exposed to physical factors) were transplanted under the renal capsule of syngeneic mice. Analysis of newly formed hemopoietic organs was performed after 3 and 5 months. The total amount of hemopoietic cells, number of multipotent stromal cells, efficiency of colony formation from these cells, and weight of bone capsule of the transplants were measured. Microscopic study showed that 5-month transplants were significantly larger than 3-month transplants and contained 3-fold more hemopoietic cells (20-fold in the AILIH+EHF group). The number of multipotent stromal cells was maximum in EHF+AILIH group (by 2.2 times higher than in the control) and minimum in AILIH+EHF group. Exposure to EHF+AILIH had most pronounced effect on the formation of the bone marrow transplants. The weight of bone capsules more rapidly increased in gelatin sponges of 3-month transplants of EHF+AILIH and AILIH groups. These data suggest that the studied physical factors can be used for acceleration of rehabilitation process.

The paper gives the results of an investigation of platelet serotonin levels in patients with tick-borne encephalitis to determine a criterion for predicting the development of its to-wave course. Fifty-five patients were examined at the height of tick-borne encephalitis (in the first 2-4 days): Group 1 included 39 patients with a one-wave course of the disease; Group 2 consisted of 16 patients with its two-wave course. Platelet serotonin concentrations were determined by enzyme immunoassay. Analysis of platelet serotonin levels could establish its lower value in the two-wave course (115.6 ± 36.2 ng/ml) than in the one-wave one (261.9 ± 96.8 ng/ml; p < 0.001). The significant difference between these types of tick-borne encephalitis and the calculation of the optimal cutoff value could propose this indicator as a predictor to detect the second wave of the infection.

The paper shows the informative value of changes in the serum levels of serotonin and high-sensitivity C-reactive protein in 44 patients in the acute period of tickborne encephalitis. Group 1 included 35 patients with non-paralytic neuroinfection; Group 2 comprised 9 patients with paralytic neuroinfection. The serum level of high-sensitivity C-reactive protein increased and that of serotonin decreased in relation to the form and severity of the disease at its height. The elevated level of the former and the low concentration of the latter may serve as an early predictor of the development of a severe paralytic form. Investigating their serum concentrations should be included into an examination plan for patients with acute tick-borne encephalitis.

Aim: Study safety, reactogenicity, immunogenicity and prophylactic effectiveness of polysaccharide pneumococcus vaccines during immunization of adult HIV-infected patients., Materials and Methods: 200 HIV-infected patients at stages 3 to 4A of the disease aged 20 to 50 years with the quantity of CD4+ T-lymphocytes in blood of no less than 500 microl(-1) took part in the study. 100 individuals immunized with polysaccharide 23-valent pneumococcus vaccine (Pneumo 23, Sanofi Pasteur, France) constituted the observation group. 100 individuals not immunized against pneumococcus infection constituted the comparison group. The groups were standardized by sex, age and disease stage. Vaccine reactogenicity was evaluated by detection of general and local postvaccination reactions, degree of their intensity and duration. Vaccine safety was evaluated based on comparative evaluation of results of general clinical and biochemical studies of blood, general urine analysis, determination of IgE in blood sera, CD4+ T-lymphocytes level, quantity of HIV RNA (viral load) before vaccination and 28 days after the immunization. Vaccine immunogenicity was evaluated by determination in blood sera of IgG against a mixture of Streptococcus pneumoniae polysaccharides comprising Pneumo 23. Prophylaxis effectiveness of the preparation was evaluated by juxtaposition of acute respiratory illness morbidity in observation and control groups., Results: During immunization of HIV-infected patients against pneumococcus infection postvaccination complications, severe local and general postvaccination reactions were not detected, laboratory studies carried out before and after the immunization gave evidence on the lack of progression of the main disease and activization of the infectious process. After the immunization the geometric mean antibody titer against S. pneumoniae increased by 2 times and reached protective level. Index of prophylactic effectiveness of Pneumo 23 vaccines during immunization of HIV-positive patients was 5.6, and relative risk of the disease in the immunized group--0.07, in the control group--0.42., Conclusion: The data provided give evidence on the high prophylactic effect of vaccination of immune compromised HIV-positive patients with a lack of deterioration of the main disease course.

The paper describes a clinical case of celiac disease with grade 3 malabsorption, which is associated with recurrent aphthous stomatitis and schizophrenia. On readmission after 8 months of strict adherence to his gluten-free diet, the patient was observed to be in clinical remission and to have normalized laboratory indices and immunological tests. The signs of recurrent stomatitis disappeared. However, the symptoms of the mental disease remained.

Aim: To elaborate recommendations for rehabilitation of patients with gluten-sensitivity celiac disease (GCD) on the basis of a long-term follow-up., Subjects and Methods: Eighty-seven patients with GCD were followed up for as long as 31 years. Of those, 72.4% of the patients kept strictly to their gluten-free diet (GFD) throughout the follow-up; 9.2% did not follow the diet periodically; and 18.4% did not at all. The sera from 71 patients were tested for IgA and IgG anti-gliadin antibodies (AGAb) and anti-tissue transglutaminase antibodies (ATTGAb) at as long as 19-year follow-up. AGAb and ATTGAb were estimated by enzyme immunoassay (IMMCO Diagnostics). All the patients underwent endoscopic and histological examinations of the small bowel mucosa (SBM)., Results: To support the validity of keeping to the GFD, the time course of clinical, laboratory, and morphological changes were analyzed in 63 and 24 GFD followers and non-followers, respectively. The GFD non-followers were more frequently found to have diarrheic syndrome, symptoms of malabsorption syndrome, lower serum concentrations of hemoglobin, total protein, iron, and calcium; no SBM structural recovery was seen in any patient. When the GFD was long adhered to, there was also a reduction in detection rates and AGAb and ATTGAb concentrations., Conclusion: The adherence to the GFD was ascertained to contribute to fuller rehabilitation in the patients. However, even the patients who had strictly kept to their GFD showed periods of an exacerbation and incomplete SBM structural recovery. Therefore, the rehabilitation system for patients with GCD must involve diagnostic, therapeutic, and organizational measures that promote not only rapid clinical recovery, but also better quality of life in these patients.

The authors presents the clinical case of autoimmune overlap syndrome: autoimmune hepatitis and primary biliary cirrhosis with outcomes in the hepatic cirrhosis complicated fatal intestinal bleeding.

Unlabelled: Adenomyomatosis (AMM) is related to the group of hyperplastic cholecystosis. Despite a long history of studying the problem, many questions concerning the etiology, pathogenesis, prevalence, tactics, management and treatment remain unsolved., Objective: To set the frequency of the AMM, its types, nature of pathological changes in the wall and lumen of gallbladder on the base of analizing the gallbladders after surgical removal., Material and Methods: ultrasound examination, macro--and microscopic evaluation of 328 cases of the AMM gallbladders., Results: According to ultrasound examination detection rate of AMM was 16.6%, and aacording to the study of surgical material--33%. The average age of patients 53 years old, male to female ratio--1:3,7. In 193 cases, the AMM was combined with concrements in gallbladder, in 70 cases the AMM was combined with polyps, among them in 40 patients the polyps were combined with concrements. In 175 patients we visualy analyzed the compaund of stones in gallbladder, in 112 cases there were the cholesterol stones (64%), in 51 cases--pigment stones (29.1%), in 12 patients (6.9%)--mixed. In some cases, was mentioned a combination of different AMM forms: adenomyoma on the background of diffuse adenomiomatosis--3.3%, diffuse form of AMM with more emphasized segmental lesions in one of the parts of gallbladder--6.1%, adenomyoma in one part combined with segmental lesions of another part of the gallbladder in 1.2% cases. In 64.9% cases, the AMM was combined with lipomatosis, in 56.7% cases--with the cholesterosis., Conclusion: The AMM is not a rare disease of gallbladder, and according to the histological examination of surgical material is detected in 31% of cases, and is oftenly combined with other types of hyperplastic cholecystosis.

The treatment policy of nutritive support for patients with different types of celiac disease is still actual issue. The difficulty of treatment policy implementation associated with villus atrophy, that brings on not only small intestine malabsorption function, but secretory process disorder (particularly, some of intestinal ferments production, including carbohydrases. The work objective is different types of celiac disease (typical, latent, torpid) nutritive correction improvement based on study of small intestine mucous membrane morphofunctional features at different stages of its atrophy, its carbohydrase activity that identifies clinic manifestation features, including nutritional disorders. We suppose, that such phermentopathy correction by means of directional action composites will have a wholesome effect on elimination of different nutritive disorder at celiac disease.

The article presents a case of 18-year follow-up of 59 y. o. patient with cholecystolithiasis and adenomiomatosis, with the development of complications of rapidly progressing xanthogranulomatous cholecystitis with malignancy.

In this article presented results of examination and treatment of 207 patients with glutensensitive celiac disease. And also you can find comprehensive method for the treatment of patients with varying severity of disease. The fundamental method of therapy glutensensitive celiac disease is strict lifelong adherence to a gluten-free diet (GFD), which eliminated protein cereal--gluten contained in wheat, rye and barley. Recently, there is large number of products which include the "hidden gluten". Its elimination from the diet of GFD is mandatory for patients with celiac disease. In the presence of diarrhea and malabsorption syndrome are used adsorbents, astringents, enzymes, intestinal antiseptic, probiotics. With the purpose of correction of metabolic disorders intravenous electrolyte mixture containing potassium, calcium and magnesium. To eliminate protein deficiency drugs used solid protein mixture of pure amino acids, gluten-free mixes for enteral feeding. Clinical examination of patients with celiac disease is aimed at monitoring compliance with GFD, early detection of cancer, autoimmune and other related diseases.

We described a patient 40 years old, admitted to the clinic with periodic attacks of pain in the right upper quadrant. With ultrasound it was confirmed chronic acalculous cholecystitis, and at endoscopy and multiple biopsies revealed atrophy of the mucosa of the duodenum (DM), corresponding to celiac disease (stage III in the Marsh classification). Titer of antibodies to gliadin (AGA) and tissue transglutaminase (AtTG) were higher: 60 and 110 units/ml, respectively, at a rate of 10 units/ml. The patient was assigned a lifetime adherence to a gluten-free diet, serologic test and a control endoscopy with biopsy at 6 months. The important role of the doctor-endoscopist in the diagnosis of latent forms of celiac disease. The significance of DM atrophy in the pathogenesis of patients with chronic cholecystitis.

In 2007-2008, the Perm Territorial Center for Prevention and Control of AIDS and Communicable Diseases investigated the efficacy of the Russian antiretrovirus drug Nikavir used in various chemoprevention (CP) regimens for perinatal HIV infection, by analyzing epidemiological findings and the results of the clinical and laboratory studies of patients. The study covered 38 HIV-infected pregnant women aged 18-32 years and their 38 born babies. From 23-32 weeks gestation to labor, the women started receiving CP using Nikavir in combination with epivir (Group 1; n = 20) and highly active antiretrovirus therapy, including Nikavir with epivir and viramune or kaletra (Group 2; n = 18). During the investigation, the viral burden (VB) and the count of CD4+ lymphocytes were determined and physical examinations were conducted to reveal therapy-induced adverse reactions. Polymerase chain reaction used to test HIV DNA in babies at 1.5 and months of life for early diagnosis of HIV infection. Both CP regimens showed a high efficiency, as suggested by no perinatal infection in the born babies, by a reduction of VB in the HIV-infected women to the undetectable level, and by an increase in the count of CD4+ lymphocytes. No adverse reactions due to the intake of the drugs were recorded.

The Purpose of the Study: Determination of the diagnostic value of ultrasound elastometry of liver (UEL) in the assessment of liver fibrosis in patients with chronic diffuse liver diseases (CDLD)., Material and Methods: The study involved 316 patients with various etiologies of the CDLD, with the underwent both liver biopsy, the UEL, and evaluation of fibrosis (F) according to the Metavir classification., Results: The maximum diagnostic accuracy of the UEL was obtained in determining of the 4-th stage of fibrosis according to the Metavir. The accuracy of the method was 91% with a sensitivity of 100%. The lowest sensitivity of the UEL determined in patients with nonalcoholic fatty liver disease (NAFLD): F1 - 25%, F2 - 33%, F3 and F4 - 50%. The High body mass index (BMI = 30,1 +/- 3,8 kg/m2) is a factor which is limiting the use of elastometry for patients NAFLD. The low sensitivity for F1 and F2 - 14,3% and 10%, respectively, 100% for F4, with a BMI = 24,4 +/- 5,1 kg/m2 was obtained in primary biliary cirrhosis (PBC). In the alcoholic liver disease (ALD) obtained high sensitivity (100%) for F2 and F4. In the CDLD of viral etiology the sensitivity of UEL was 33-71,4% in the early stages of fibrosis (F1 and F2) with high specificity - 100% and 93.5% respectively., Conclusion: The use of the UEL allows the diagnosis of fibrosis in chronic liver diseases of different etiologies as an alternative to needle biopsy of the liver.

The incidence of celiac disease in the elderly patients in recent years is increasing and is 7.2% of all examinees. More than half of patients with onset of the disease is characterized by severe malabsorption syndrome III degree and is diagnosed in a short time from the first signs of illness. The rest of celiac disease occurs in small symptom long form, so that the diagnosis was first established over 10 years and over from the beginning of the disease. Late diagnosis of celiac disease in the elderly patients, and hence non-gluten-free diet increases the risk of complications such as cancer.

The paper describes a clinical case of gluten-sensitivity celiac disease (GSCD) and recurrent lower extremity vein thrombosis in a female patient. According to the data available in the literature, GSCD is associated with increased risk for thrombosis. Hyperhomocysteinemia and protein S, folates, and vitamin B, 2 deficiencies may be responsible for thrombophilia in GSCD. Moreover, GSCD may be associated with antiphospholipid syndrome.

Aim: To assess sensitivity and specificity of phosphorescent immunochips developed by the authors on the basis of microplate phosphorescent assay (PHOSPHAN) for detection of IgM and IgG antibodies to tick-borne encephalitis virus (TBEV) in sera of patients and to compare results of PHOSPHAN assay with results obtained by lanthanide immunofluorescence assay (LIFA) and solid-phase enzyme immunoassay (SPEIA)., Materials and Methods: Two hundred sixty one serum samples were tested, including 155 samples from 74 patients with clinical diagnosis of TBE confirmed by serologic identification of IgM antibodies to TBEV. Sera were collected in 2003 in Perm region from persons, which fell ill during seasonal increased activity of ticks-vectors of TBEV, as well as from healthy blood donors. Phosphorescent immunochip corresponds 96-well plate with 4 active microzones formed on the bottom of each well, which are able to detect specific IgM and IgG antibodies to TBEV. Immune reaction was visualized by conjugate of streptavidin with Pt-coproporphyrin. Intensity of fluorescence was measured by scanning the bottom of previously dried microwell with scanner IFI-02., Results: Comparable sensitivity and specificity of POSHPHAN assay, LIFA and SPEIA was demonstrated for detection of IgM and IgG antibodies to TBEV in samples. Immunoluminescence-based PHOSPHAN assay and LIFA were more sensitive for analysis of sera with low titer of specific IgM antibodies., Conclusion: PHOSPHAN assay could be used for early serologic diagnostics of TBE as well as for assessment of antibody level for control of efficacy of treatment in patients with prolonged illness or level of protective immunity in vaccinees.

The efficiency of correction of cytokine disbalance and peptic ulcer regeneration has been studied using the model of chronic peptic ulcer at use based on mononuclear fraction cells (MFC) of autologous bone marrow (BM). MFCs are shown to remove cytokine disbalance, reduce systemic inflammation reaction and accelerate peptic ulcer regeneration.

During spring-autumn period of 2006 Borrelia were isolated for the first time in Russia from blood of 79 patients treated in Perm City Clinical Hospital for Infectious Diseases No. 1 with diagnosis "tickborne borreliosis, manifestive form with migrating erythema, localized stage". Ten primary isolates (12.7% of total seeded samples) were obtained by seeding plasma samples on the BSK medium. Their subsequent identification by polymerase chain reaction-restriction fragments length polymorphism revealed presence of Borrelia garinii NT29 in all patients. Length of sequenced fragment of rrfA-rrlB region was 253 b.p. Seven isolates had 100% and 3 - 99.6% similarity with typical strain NT29 (L30130). Nucleotide sequences of 4 obtained isolates were deposited in GenBank database (No. AM932199 - AM932202). It was proposed that B. garinii NT29 more frequently than other Borrelia species can be an etiologic agent of tick-borne borreliosis not only in Perm region but also in whole Russia.

Possibility to use blood dried on filter paper for serological testing on antibodies to tick-borne encephalitis (TBE). Sensitivity and specificity of specific IgM detection in dry stains of blood by lanthanide fluorescence immunoassay was 94.9% (86.9-100%) and 97.5% (94-100%) respectively, compared with results obtained in tests of sera. Agreement in positive and negative results of tests for IgM against TBE in 562 serum samples and dry blood stains was 95.3%. During analysis of both types of biomaterial high degree of correlation was observed between intensity of fluorescence when testing for both IgM (r=0.86700; p=0.05; n=562), and IgG (r=0.83883; p=0.05; n=337) toTBE virus. Use of this mildly invasive technique of blood draw is reasonable during conduction of large-scale population studies for seroepidemiologic monitoring, investigation of disease outbreaks, control of effectiveness of vaccination against TBE, assessing of level of specific immunity in population of endemic regions, control of treatment, and serologic diagnostics of acute TBE in hospitalized patients, in which blood draw is difficult to perform.

The diagnosis and treatment of patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) by local physicians of one of the large administrative districts of Moscow were examined. Nine hundred and sixty outpatient's cards at 22 polyclinics were randomly checked up. There was a high percentage of diagnostic and therapeutic errors, the main reason for which was therapists' inadequate training in pulmonology. After implementing the intensive educational programs on BA and COPD for a year, a reexamination showed a considerable reduction in the number of medical errors.

The PCR and sequence analysis revealed DNA Ehrlichia muris, Anaplasma phagocytophilum, and Rickettsia spp. in the I. persulcatus ticks and blood samples from a patients with acute febrile illness occurring after a tick bite, registered in the seasonal peak of the tick activity of one of the highly endemic areas of Russia (Perm region). These data confirmed the validity a diagnosis of HME and HGA, which were made earlier on the basis of the clinical-serologic survey. In 10.0% of the tested taiga ticks were detected DNA of two and more agents in various combinations i.e. E. muris and Rickettsia spp, A. phagocytophilum and Rickettsia spp., and E. muris, A. phagocytophilum and Rickettsia spp. DNA of a R. helvetica was detected in I. persulcatus tick and blood tick-bitten patient with febrile episodes. Probably that R. helvetica can be etiological agent in some part of cases with the serologically unconfirmed diagnoses of acute feverish diseases developing after tick bite.

New drug formulation--a sublingual tablet--was developed on the basis of human leukocyte interferon (HLI). Evaluation of antiviral and immunomodulatory effects of the new formulation of HLI in patients with influenza showed its efficacy. The drug shortened duration of intoxication and catarrhal syndrome, decreased rate of complications and restored interferon status. Obtained results showed that "Interferon tablets 4000 IU" can be used in complex treatment of patients with influenza.

Glandular cystic ovarian endometriosis (OE) is characterized by a more intensive blood supply than cystic OE. This type of OE is characterized by a high proliferative glandular epithelial activity detected by an immunohistochemical study using antibodies to PCNA and CA-125. Moreover, a positive correlation is found between the serum concentration of CA-125 and the expression of this antigen in the epitheliocytes of an endometrioid cyst in both glandular-cystic and cystic OE. Thus, the findings permit the determination of the morphofunctional activity of a type of OE and its aptness to the progression of the disease and to the development of recurrences.

Lanthanide immunofluorescence assay (LIFA) was used to detect IgM of antibodies to tick-borne encephalitis (TBE) virus in 791 patients who had been fallen ill with acute febrile diseases in the period of seasonal activity of carrier ticks in the endemic region of Russia (the Perm Region) (1786 sera being tested). This assay was equally effective as the commercial enzyme immunoassay test system (EITS) in the early serological diagnosis of TBE, verifying the clinical diagnosis in about 70% of patients just within the first week of disease. At the same time, the sensitivity of LIFA was much (nearly 5 times) higher than that of EITS in revealing antibody IgM in patients with chronic TBE, as well as in those with the acute course of disease, accompanied by the low level and untypical trend of accumulation of antibodies ofthis class.

Analyzing the clinical observations of 1343 patients, made in the Kama river region in 1991 to 2002, could establish a number of characteristic syndromes of the acute period of Ixodes tick-borne borreliotosis (ITBB). The early period of the diseases manifested itself as two forms: erythematous in 1041 (77.5%) patients and erythema-free in 302 (22.5%). The erythematous form was characterized by the occurrence of the major clinical marker--erythema migrans at the site of tick suction. In Russia, the clinical features of the acute phase of borreliotosis were marked by the early (at weeks 2-3 of the disease) affliction of different organs (the liver) and systems (the nervous, cardiovascular, and locomotor ones). The leading clinical types of the erythema-free ITBB were neurological, arthromyalgic, influenza-like, cardiovascular, hepatitis, regional lymphadenitis, and mixed. The diagnosis of ITBB is established on the basis of a characteristic epidemiological history, clinical manifestations by taking into account the most common types of its early period and the data of a serological survey by the proposed algorithm.

Serological and epidemiological surveys covered 2407 persons in 20 populated localities situated in all large geographical and regional subdivisions (subzones) in the Perm Region. Indirect immunofluorescence tests revealed serum immunoglobulins to Borrelia burgdorferi sensu lato. Antibodies in 1:40 or higher dilution were found in nearly 5 to 11% of the dwellers of localities in the subzones of south taiga, coniferous broad-leaved forests, and forest steppe; about 3-7% and 1-6% of them were present in the populations of mountain and middle taigas, respectively. According to the frequency of tick suction and the proportion of an immune interlayer among the population within the Perm Region, four districts were identified by varying risks for infection (epidemic hazard) with Ixodes tick-borne relapsing fever. The populations living in the subzones of south taiga, coniferous, broad-leaved forests, and forest steppe run the greatest risk. An area at average infection risk area corresponds to the south part of a mountain taiga subzone and that at lower risk does to the south part of a middle taiga subzone. There is no possibility of relapsing fever contamination outside the area of Ixodes persulcatus ticks at all. Comparison of their own findings and official statistics has made the authors conclude that there is a great hyperdiagnosis of relapsing fever in the region in question.

Bubo-M, the first Russian combined vaccine, was found to have low reactogenicity. The difference between the number of postvaccinal reactions in the group of children immunized with Bubo-M (25.9%) and those in the group of children who had been simultaneously injected into different sites of the body with ADS-M toxoid (adsorbed DT toxoid with reduced antigen content) and hepatitis B vaccine (26.7%) was not statistically significant. Following immunization a considerable increase in the level of diphtheria and tetanus antibodies (p < 0.005) was observed in all children (100%), the level of HBs antibodies in the group of children immunized with Bubo-M (the geometric mean titer: 13,721 IU/l) essentially exceeding that observed in the control group injected with ADS-M toxoid and hepatitis B vaccine (the geometric mean of the titer: 2,441 IU/l). Bubo-M was duly registered and allowed for industrial production and medical use.

Bubo-M, the first Russian associated vaccine, was found to have low reactogenicity and high immunogenic potency. The frequency of postvaccinal reactions in the group of persons immunized with Bubo-M (20%) appeared to be considerably lower than among persons who received the combined injection of adsorbed DT toxoid with reduced antigen content and vaccine against hepatitis B (47.7%). Following the course of vaccination the level of anti-HBs considerably exceeded the protective level. Immune response to the diphtheria and tetanus components of Bubo-M exceeded that observed after immunization with absorbed DT toxoid with reduced antigen content (p < 0.05).

Three hundred and seventy one sera sampled in different period since the onset of the disease from 214 patients with Ixodes tick-borne borreliosdes (ITBB) caused by Borrelia afzelii and B. garinii in the Perm Region (Russia) and 299 sera from 222 patients with other diseases were simultaneously tested for IgM and IgG antibodies by using immunofluorescence assay (IFA) with standard antigen from strain Ip-21 B. afzelli by indirect micromodification of enzyme immunoassay (IMELISA) on slides and routine enzyme immunoassay (ELISA) with standard commercial test systems (Medipan Diagnostica GmbH, Germany). It is concluded that IMELISA is a technically easy and accessible test, which is close to IFA in its specificity and sensitivity, and can be widely used for serological verification of ITBB.

Serological verification of ixodid tick-borne borrelioses (TBB) is carried out in Russia by using IFA with the standard antigen prepared from the strain Ip-21 B. afzelii by the Laboratory of Infection Vectors, Gamaleya Research Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences. This study is under way at approximately 50 research and practical institutions that are situated in 30 large administrative territories of the country. The nIFA data on 371 sera from 214 patients with TBB and 229 sera from controls who had other infections have been analyzed. Changes in the proportion antibody sera, mean geometrical and cut-off antibody titers in patients with TBB were compared with those in the controls. The values of seroconversion were analyzed in relation to the time lasted after the onset, the first serum collection, and an interval of reexamination. The specific results of tested of the coded sera were obtained during the international interlaboratory blind experiment. It is concluded that nIFA yields results that are suitable for TBB verification.

Patients with erythematous Ixodes tick-borne relapsing fever were examined and their skin biopsy specimens were morphologically studied to reveal clinical, immunological and morphological features of erythematous Ixodes tick-borne relapsing fever. Two types of development of erythema migrans were identified. These include 1) a typical type that appears as an area of homogenous hyperemia or that of annular shape and 2) an atypical one that presents as minor vesicles. There were elevated serum immunoglobulins A levels at the height of the disease. Morphologically, at the early stage of the disease, the center of erythema shows disturbances characterized by epidermal dystrophic processes, koilocytosis, subhorny and epidermal vesicles. The dermis displays solid perivascular lymphocytic infiltrates admixed with fibroblasts, fibrocytes, macrophages, plasmocytes, eosinophils, degranulated labrocytes. The interstitium exhibits scanty infiltrates. These changes are less pronounced at the periphery. Electron microscopy shows the structures morphologically similar to those of Borrelia. The late stage (days 15-23) of the disease is marked by insignificant dystrophy and perivascular fibrosis. There were no interstitial infiltrates. By and large, the pattern of clinical and immunological manifestations in patients with erythema migrans correlates with dermal morphological changes.

327 Borrelia isolates from ixodid ticks of 3 species from 12 major administrative territories of Russia (from Leningrad Province in the west to Sakhalin Province in the east), as well as from forest myomorph rodents of 6 species and from skin biopsies of borreliosis patents, were identified by the PRC and RFLP methods. B. afzelii, B. garinii and B. garinii NT29 were shown to be widespread in Russia. No other Borrelia genospecies were found. The main vectors of B. afzelii and B. garinii were ixodid ticks Ixodes persulcatus and I.ricinus and their main reservoir hosts were forest myomorph rodents. In natural foci Borrelia mixed infection was observed among reservoir hosts and vectors. This determines the possibility and considerable probability of human infection caused by several Borrelia genospecies simultaneously.

Previous studies indicated that in the Perm Region there are two pathogen species: B. garinii and B. afzelii which cause the disease mainly with neurological and dermatological manifestations. In 1990-1994, in the Perm Region 646 patients with Ixodes tick-borne borreliosis (ITBB), including 535 with erythema migrans, 54 without it, and 57 with late chronic disease were studied. Damages to the central and peripheral nervous systems were detected at all stages of an infectious process. The prevalent clinical manifestations are encephalitis, encephalomyeloradiculoneuropathies, mono- and polyneuropathies. These abnormalities are more frequently formed in patients with its erythema-free type both in the acute period of the disease and in the late period of infection. A varying spectrum of neurological syndromes and their significant incidence determine the resemblance of ITBB in Russia and West Europe. The clinical findings are in good agreement with the results of etiological structural studies of ITBB in the region.

A special epidemiological experiment to prevent borreliosis in persons bitten by infected ticks was performed in 1992-1994 in the Russia's Perm region where Borrelia garinii and B.afzelii circulate, and Ixodes persulcatus tick is the sole vector transmitting these pathogens to human beings. Adult ticks were removed from the bodies of persons who had referred to health facilities for first aid. Vital preparations were made from the material obtained from the gut of each tick and examined microscopically (up to 250 microscopic fields per preparation). The patients bitten by infected ticks were divided into experimental and control groups and kept under special medical and serological control for 4-5 months. The patients of the experimental group received doxycycline (100 mg twice daily) for 3-5 days after ticks had bitten. Borreliosis was diagnosed by a combination of clinical and serological data. The control group consisted of 97 patients who took no antibiotics after ticks biting and 12 of them contracted borreliosis. In 823 cases Borrelia were not revealed while microscopically analyzing the ticks removed from the patients' bodies; in this group six patients contracted borreliosis. The morbidity rate (per 100 patients) in the experimental group was 1.1, i.e. 11 times lower than that in control group. Among the patients bitten by infected ticks and untreated with antibiotics, this index was 17.6 times higher than in the group bitten by ticks in which Borrelia were not found. There is no absolute probability of detecting the pathogen during a direct microscopic analysis of the preparation made from the tick removed from the body of a bitten patient. However, this rapid identification of Borrelia, followed by short-term antibiotic treatment for microbiological evidence is an effective tool for preventing patients from contracting borrelioses.

The territory of the Perm region is highly endemic in Ixodes (B. garinii and B. afzelii)-borne borreliosis. The clinical manifestations of erythema-less Ixodes-borne borreliosis were studied in the 1991-1994 epidemiological seasons. A total of 54 patients were examined in the acute stage of infection and 4-6 months later. There were common symptoms of damage to the central nervous system in early infection and pronounced signs of damage to the central and peripheral nervous systems in the late period which was characterized by cardiovascular diseases as disturbances of automatism functions, conduction, diffuse and local muscle changes.