Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Morphofunctional State of the Ovaries in Rats with Experimental Model of Functional Cysts and Their Treatment with Gonadotropin-Releasing Hormone Antagonist.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly (p=0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

[Sanatorium-and-spa treatment of patients who have had a new coronavirus infection (COVID-19)]. / Sanatorno-kurortnoe lechenie patsientov, perenesshikh novuyu koronavirusnuyu infektsiyu (COVID-19).

PURPOSE OF THE STUDY: Evaluation of the effectiveness of sanatorium-and-spa treatment of patients who have undergone a new coronavirus infection (COVID-19), taking into account the polymorphism of symptom complexes. MATERIAL AND METHODS: The study included 56 patients (22 men, 34 women; mean age 64.9±8.21 and 64.76±9.12 years, respectively) who had COVID-19 and were treated at a spa. The mandatory program of rehabilitation and rehabilitation sanatorium treatment included: exercise therapy with elements of breathing exercises, general massage with an emphasis on the chest, halo and speleotherapy, hydrotherapy, inhalations, as well as psychotherapeutic methods. The length of stay in the sanatorium was at least 2 weeks. We assessed the dynamics of indicators characterizing the activity of the cardiovascular and respiratory systems (BP, heart rate, Stange test), exercise tolerance (6-minute walk test), as well as psycho-emotional state (test «Health, Activity, Mood¼, SAN) up to and after treatment. RESULTS: Against the background of sanatorium-and-spa treatment in patients who underwent COVID-19, the number of complaints significantly decreased: in men from 6.2±2.4 to 3.4±1.3, in women from 7.7±1.5 to 4.12±1.5 (p≤0.05). A similar dynamics of indicators characterizing the activity of the cardiovascular system was noted: the level of systolic blood pressure in men decreased by 7.3%, in women - by 10.3%; the level of diastolic blood pressure - by 4.1 and 1.4%, respectively. Heart rate in men decreased from 83.69±15.2 to 75.54±12.24 beats/min; in women - from 92.16±14.16 to 76.4±11.68 beats/min. The distance traveled for men (6-minute walk test) increased from 384.15±108.78 to 408.92±97.30 m; in women - from 371.84±75.9 to 397.12±76.2 m (p≤0.05). The breath holding time on inspiration (Stange test) in men increased from 38.00±10.64 to 45.69±9.51 s; in women - from 39.96±9.31 to 43.60±6.93 s. The values of the «Well-being¼ indicator (SAN test) in men significantly increased - from 4.5±1.8 to 5.1±0.9 points (p≤0.05); «Activity¼ - from 4.8±0.8 to 5.4±0.5 points (p≤0.05); «Mood¼ - from 4.7±1.4 to 5.4±0.6 points. Similar dynamics were observed in women. CONCLUSION: Against the background of the sanatorium stage of treatment, a stable positive dynamics of the indicators of the functional state of the body was noted in both men and women. The analysis carried out confirms the need to develop and implement rehabilitation programs in sanatorium-resort conditions for patients who have had a new coronavirus infection.

[Medical rehabilitation of children with bronchial asthma]. / Meditsinskaya reabilitatsiya detei s bronkhial'noi astmoi.

Medical rehabilitation of children suffering from bronchial asthma is based on the complex use of natural therapeutic factors, drug, non-drug therapy and other methods in order to achieve control over the disease and long-term remission. The use of non-drug technologies is necessary taking into account the pathogenesis of the bronchial asthma development and is aimed at relieving bronchospasm, reducing the activity of allergic inflammation in the bronchi, improving their drainage function, strengthening the respiratory muscles and increasing exercise tolerance. When carrying out rehabilitation measures it is important to observe the basic principles of medical rehabilitation. An individual medical rehabilitation program is drawn up taking into account the assessment of the child's clinical condition at each stage with the diagnosis of the initial rehabilitation status, the establishment of a rehabilitation diagnosis and an assessment of the rehabilitation potential. The article presents the data of the analysis of scientific publications and our own research allowing to draw up an algorithm for the formation of an individual program of medical rehabilitation for children with bronchial asthma.

PCR-based diagnosis of whooping cough in the Russian Federation.

The aim was to determine how often the PCR method is used in different laboratories in Russia. In 2018, we conducted a questionnaire survey in diagnostic laboratories of medical organizations and the Centers of Hygiene and Epidemiology that performed PCR studies to identify microorganisms of the genus Bordetella in all 85 Russian regions. We found that in 2013 the PCR was used in 33 (38.8%) regions, but in 2017 the number of regions increased to 64 (75.3%). During 2013-2017 the study has not been applied in 21 regions. The number of PCR tests performed in the laboratories of medical organizations was significantly different. There has been an increase in the number of tests for the diagnosis of pertussis among people with clinical signs of infection and among contact persons in foci of infection. Compared to the Centers of Hygiene and Epidemiology, in medical organizations the rate of introduction of the PCR was higher. Between 2013 and 2017 the proportion of samples containing DNA B.pertussis decreased, but the proportion of samples containing DNA of other representatives of the genus Bordetella increased. Moreover, in the case of isolation DNA Bordetella spp. clinicians diagnose «Whooping cough, other unspecified organism¼, since there is no information on the species of the pathogen. Thus, in order to improve the diagnosis of pertussis, it is necessary to optimize PCR tests by including target genes that allow to identify of currently relevant DNAs of different representatives of the genus Bordetella.

[Chromoblastomycosis]. / Khromoblastomikoz.

The paper describes a case of chromoblastomycosis, a rare implantation mycosis in the Russian Federation. It gives data on the prevalence, etiology, and clinical presentations of the disease, and the diagnostic possibilities. Emphasis is laid on the leading role of a pathomorphological study in the diagnosis of chromoblastomycosis in non-endemic countries, including Russia. The clinical and pathomorphological presentations are described in detail. Histological examination detected 5-12-µm spherical or polygonal pigmented cells that are fungal elements, which allows chromoblastomycosis to be diagnosed in the cytoplasm of macrophages and extracellularly. A refusal to conduct a pathomorphological study leads to diagnostic errors and an irrational treatment policy.

Development of accelerated genodiagnosis method of pertussis and pertussis-like diseases on the basis of mPCR-RT.

The aim of the work was to develop an accelerated genodiagnosis method based on mPCR-RT for the detection DNA of B. pertussis, B. parapertussis, B. holmesii. MATERIALS AND METHODS: The study used 104 strains of microorganisms, of which: 50 strains of B. pertussis, 37 - B. parapertussis, 17 - heterologous species of microorganisms. Assessment of analytical specificity was carried out using DNA strains of various microorganisms with a concentration at least 109 GE / ml. To check the analytical sensitivity we studied a series of serial dilutions of bacterial cultures of the control strains B. pertussis № 143, B. parapertussis № 38b, B. holmesii DSM 13416 with a concentration of 5x109 - 5 µm/ml. RESULTS: Insertion sequences were chosen as diagnostic targets: for B. parapertussis - a specific fragment IS1001, for B. holmesii - a specific fragment hlIS1001, for B.pertussis - a fragment IS481. To develop a genodiagnosis method specific primers were designed and combined into a single multi-primer mixture, the composition of the reaction mixture and the amplification conditions were selected. The analytical sensitivity of the developed method for detecting pertussis and pertussis-like pathogens was 5×101 GE / ml. Verification of the developed methodology of gene diagnostics showed 100% analytical specificity. CONCLUSION: An accelerated genodiagnosis method based on mPCR-RT has been developed, it allows you to identify DNA of B. pertussis, B. parapertussis, B. holmesii, which expands the possibilities of examining patients with suspected pertussis and pertussis-like diseases in order to increase laboratory confirmation of the diagnosis.

[Serological diagnosis of pertussis in older persons.] / Серологическая диагностика коклюша у лиц старшего возраста.

The aim of the work was to assess the effectiveness of serodiagnosis of pertussis in people over 50 who complained of prolonged cough. The study included 30 patients over the age of 50 who applied to the consultative diagnostic center complaining of a prolonged cough in the period from 2015 - 2020. Blood serum samples were investigated in enzyme immunoassay with the definition of antitussive antibodies of three classes - IgM, IgG, IgA in the commercial test system RIDASCREEN (R-Biopharm AG, Germany). It was found that in the serum samples of individuals over the age of 50, IgM antibodies above the threshold level were not detected. Patients were divided into two groups - with IgG and IgA antibodies above the threshold level (group 1) and below the threshold level (group 2). In the first group, in 83.3% and 61.1% of patients, the levels of antibodies of the IgG and IgA class significantly exceeded the threshold level (189.8 ± 16.7 U / ml and 290 ± 20 U / ml, respectively), which indicated a pertussis infection; in 5.6% and 38.9% of patients, IgG and IgA class antibodies slightly exceeded the threshold level (20 U / ml and 43 ± 2.3 U / ml, respectively), which indicated a dying infection. In the second group, in 100% of patients, antibodies of the IgM and IgA classes were determined below threshold levels, and IgG antibodies were detected in 58.3% of individuals at low rates, which corresponded to the natural immunological background of individuals not infected with pertussis pathogen. Therefore, in the presence of a prolonged cough in adults, it is advisable to study blood serum samples for the presence of antitussive antibodies of three classes, which is especially important when people of older age live in families with young children and pregnant women.

[Comparison of rayon and flocked swabs for collection and transport of deep throat swabs for detection of bacteria causing whooping cough by multiplex real-time PCR assay.]

The aim of the work was to comparison of rayon and flocked swabs for collection and transport of deep throat swabs for detection of bacteria causing whooping cough by multiplex real-time PCR assay. The study included 87 patients aged from 1 month to 37 years, hospitalized in Infectious Diseases Clinical Hospital No. 1 of the Moscow Department of Healthcare. 68 (78,2 %) people had a diagnosis of whooping cough, the main group of which consisted of children aged 1 to 12 months (median 4 months); 17 (19,5 %) - other diseases of the respiratory tract; 2 (2,3 %) - contact with sick whooping cough. The initial examination of patients was carried out on the 1 - 8th week of the onset of the disease. The material from the patients was taken at one-day interval with commercial rayon swabs and flocked swabs. Identification and differentiation of specific genome fragments of the causative agents of whooping cough in biological material was carried out by real-time PCR using the «AmpliSens® Bordetella multi-FL¼ reagent kit. The efficiency of PCR-based diagnostics of whooping cough using flocked swabs at the preanalytical stage was 83,8 %, and rayon swabs - 82,3 %. The use of a flocked swabs at the preanalytical stage increased the research efficiency by 1,5 %. Thus, when collecting biological material for PCR-based diagnostics of whooping cough it is possible to use flocked swabs.

[Definitionof anti-pertussis antibodies by immunoassay.]

Comparative analysis of efficiency of identification the anti-pertussis of antibodies of three classes (IgM, IgG, IgA) by means of four commercial test systems used for serological diagnosis of whooping cough in the Russian Federation by RIDASCREEN (R-Biohharm AG, Германия), NOVATEC (Immunodiagnostica GmbH, Germany), DRG Diagnostics (Germany), Savyon Diagnostics (Israel) is carried out. The research included 42 serums of blood of the children and adults with whooping cough hospitalized in Infectious diseases clinical hospital No. 1 of the Moscow Department of Healthcare. In work the commercial test systems - RIDASCREEN (r-Biofarm, Germany), NOVATEC (Germany), DRG (Germany), Savyon (Israel) are used, according to instructions of producers. Complete coincidence of results of a research is established in 40,5% cases, in 42,9% not complete coincidence of results on dynamics of development of one class of antibodies is revealed and in 9,5% cases the discrepancy of results on two classes of antibodies is revealed. In total discrepancies of results - 7,1%. At determination of antibodies of the class IgM in serum of blood of patients with whooping cough the greatest number of positive results is defined in the SAVYON - 83,3±6,3% (35 serums), NOVATEC - 71,4±8,2% (30 serums), RIDASCREEN - 61,9±9,7% (26 serums), DRG - 45,2±11,7% (19 serums). Class IgG antibodies in all test systems were defined at one level. Some distinctions took place in determination of IgA. The high percent of identification of IgA was in the RIDASCREEN - 59,5±10,0% (25 serums) and DRG - 50,0±11,2% (21 serums). In the NOVATEC and SAVYON this percent was lower - 45,2±11,7% and 26,2±13,9%, respectively (19 and 11 serums). Thus, the research showed that for serological researches any of these 4 test systems can be used. It is recommended to conduct diagnostic testings of serums of blood in one chosen test system for obtaining comparable results and to interpret the results received in one test system when obtaining doubtful results it is necessary to investigate serums in dynamics at the same time in one test system.

[COMPLEX IMMUNOGLOBULIN PREPARATION FOR THERAPY OF PERTUSSIS IN YOUNG CHILDREN].

AIM: Study the possibility of inclusion of complex immunoglobulin preparation (CIP) pos- sessing specific activity against pertussis exotoxins into complex therapy of pertussis infection in young children. MATERIALS AND METHODS: -2 groups of children with.pertussis younger than 3 years were examined. The main group (50 individuals) received CIPper os - 1 dose 1 - 2 times per day for 5 days, comparison group (34 children) received only basic therapy. Evaluation of clinical effectiveness of CIP was carried out, the content of anti-pertussis class G antibodies and total IgE in patients were studied. RESULTS: A good clinical effectiveness of the preparation was shown, as well as immune modulating activity against humoral immune response to pertussis infection. CONCLUSION: The detected positive effect of CIP on pertussis -course in children has indicated a principally novel use of this per oral drug form.

Preventive Salpingectomy and Ovarian Reserve: Experimental Study.

The levels of anti-Müllerian hormone, follicle-stimulating hormone, and testosterone were studied in rats after removal of the uterine horns, oviducts, or combined surgery. The effects of preventive salpingectomy on ovarian reserve were studied. After preventive salpingectomy, the level of anti-Müllerian hormone was low throughout the experiment, follicle-stimulating hormone increased only by the end of observation (on day 40), and testosterone level decreased only on day 10. Hysterectomy alone caused no changes in the concentrations of the studied hormones on day 10 after surgery. Salpingectomy alone reduced the concentrations of anti-Müllerian hormone and testosterone and did not change the level of follicle-stimulating hormone during this period.

[Combined treatment of palmoplantar syndrome in patients under antitumor therapy].

Observation covered 12 patients under various antitumor medications. Group 1 was formed of patients with developed palmoplantar syndrome varying in severity, who received complex treatment including IR-therapy and local antioxidant medication. Group 2 included patients without palmoplantar syndrome, who received preventive treatment with IR-therapy. All patients of group 1 demonstrated lower severity of palmoplantar syndrome manifestations. In group 2, 80% of the patients avoided palmoplantar syndrome development, and 20% of the patients had light course of the syndrome manifestations. Patients at high risk of palmoplantar syndrome under antitumor therapy are recommended to undergo IR-therapy and local antioxidant medication.

[Clinical features of pertussis in adults].

AIM: To study the clinical features of pertussis in adults. SUBJECTS AND METHODS: The clinical manifestations of pertussis in adults were analyzed in 62 patients treated in the Core Unit and Obstetric Unit, Clinical Infectious Diseases Hospital One, Moscow Healthcare Department, in 2011-2013. RESULTS: Investigations conducted in the familial foci of pertussis showed that its incidence rate was 23.7 and 10% in adults and in pediatric institutions, respectively. The source of infant infection was adults in almost one third of cases, mothers in 72% and fathers in 27.7%. Assessment of the symptom complex of pertussis in the sick mothers in the observed period ascertained that 94±3% had experienced the typical form of whooping cough: 72.0±5.7 and 22.0±5.3% had its mild and moderate forms, respectively. The disease had run a latent course in 6±3% of the patients. The paper describes cases of pertussis in 5 pregnant women admitted to the obstetric unit for complaints of persistent cough. The diagnosis of whooping cough in all the cases was based on clinical and epidemiological findings and serological tests showing specific IgA and IgG antibodies. Three and two patients experienced moderate and mild pertussis, respectively. CONCLUSION: Pertussis now remains one of the infectious diseases relevant not only to a pediatric population, but also to an adult one. Adult pertussis maintains the main clinical features typical for this infection with a predominance of its mild forms, which makes its diagnosis difficult. A serological test (enzyme immunoassay) is of high diagnostic value for verifying whooping cough in adults under the present conditions.

[Extracorporeal shock wave therapy in athletes with degenerative and dystrophic disorders of locomotory system].

Degenerative and dystrophic changes of joints and ligaments are among the most prevalent disorders in professional athletes. Specification of a complex system for these diseases is an important task in sports medicine. Extracorporeal shock wave therapy is a modern and highly effective method of rehabilitation.

[Increased functional resources in athletes of cyclic sports].

The article covers individual coaching program specified by specialists in Sports Medicine and Rehabilitation Center in Bournazian FMBC of the FMBA of Russia, to improve functional durability of highly qualified athletes.

[Isotypes of anti-pertussis antibodies in pertussis patients at different stages of the disease].

AIM: Evaluation of anti-pertussis antibodies in pertussis patients at different stages after the onset of the disease. MATERIALS AND METHODS: Levels of IgG, IgG1, IgG2, IgG3, IgG4, IgA and IgM antibodies against the antigen complex of pertussis were evaluated by enzyme immunoassay (EIA). Sera samples were analyzed from 208 pertussis patients examined from week 1 to 10 after the onset of the disease. RESULTS: 51%, 82% and 86% pertussis patients, and 67%, 72% and 78% patients examined from week 1 to 3 after the onset of the disease had increased levels of IgM, IgA and IgG antibodies respectively. 85%, 70%, 74% and 68% pertussis patients, and 76%, 57%, 87%, 57% patients examined from week 1 to 3 after the onset of the disease had increased IgG1, IgG2, IgG3 and IgG4 levels respectively. 92% of all examined pertussis patients and 83% of patients examined from week 1 to 3 after the onset of the disease had an overall increase of anti-pertussis antibody levels. Increased level of IgM antibodies was detected predominately from week 1 to 5 after the onset of the disease. Most of the patients examined from week 3 to 10 after the onset of the disease had increased levels of IgA, IgG, IgG1, IgG2 and IgG4 antibodies, and IgG3 antibody level was increased predominately in patients examined from week 2 to 6 after the onset of the disease. CONCLUSION: Serological indicators of pertussis measured by EIA were observed in 83% of the patients examined at the early stages after the onset of the disease. Simultaneous measurement of IgA, IgG and IgM antibody levels is the most effective approach for serological diagnostics of pertussis due anti-pertussis antibodies isotype composition heterogeneity at different stages after the onset of the disease. Increased levels of IgM and IgG3 antibodies are serologic indicators of the acute phase of pertussis infection.

[A direct accelerated method for detection of a whooping cough pathogen].

The developed direct method for the laboratory diagnosis of pertussis, which is based on isothermal amplification technologies, has a high (100%) specificity and sensitivity (102 m.cl.), can detect the pathogen of the disease just in the clinical sample from a patient within 7-8 hours after start of the study. The clinical trials conducted at Infectious Diseases Hospital One (Moscow) on examination of 103 patients (63 patients with the clinical diagnosis of pertussis and 40 with other respiratory tract diseases) provided evidence its high specificity and diagnostic efficiency as compared with a bacteriological test, the efficiency in different clinical types of the disease and during examinations of patients in different periods after the onset of the disease, as well as during examinations of patients with suspected pertussis and pertussis-like diseases.

[Distribution of specific IgG subclasses in patients with pertussis and in healthy persons].

AIM: To assess level of IgG1, IgG2, IgG3, and IgG4 to complex of antigens of Bordetella pertussis in patients with whooping cough and healthy children and adults. MATERIALS AND METHODS: Levels of anti-pertussis IgG subclasses in sera of patients with pertussis and healthy children and adults were measured with solid phase immunoenzyme assay using peroxidase-conjugated monoclonal antibodies to human IgG1, IgG2, IgG3, and IgG4. RESULTS: In patients with pertussis, IgG1-IgG3-IgG2-IgG4 type of distribution of subclasses with predominance of IgG1 and IgG3 was revealed. In healthy children and adults the character type of subclasses distribution was IgG1-IgG2-IgG4 with absent or low level of IgG3. CONCLUSION: Detection of specific IgG3 mainly in patients with pertussis allows to consider them as a reliable serological sign of pertussis infection.

[Improvement of pertussis diagnostics in adults with prolonged cough].

AIM: To study clinical and laboratory data and levels of IgG, IgG1, IgG2, IgG3, IgG4, IgA and IgM to Bordetella pertussis complex of antigens in adults with prolonged cough. MATERIALS AND METHODS: Antibody levels to Bordetella pertussis complex of antigens were measured by solid phase immunoenzyme assay. Clinical and laboratory methods included CBC, chest X-ray, measurement of respiratory function, allergologic tests. RESULTS: In 16 out of 75 studied patients (21%) serological signs that are characteristic for current pertussis infection (increased levels of specific IgG and IgA as well as IgG1 - IgG3 - IgG2 - IgG4 type of distribution of specific IgG subclasses) were observed. Clinical and laboratory parameters--course of disease, characteristics of cough, results of CBC--corresponded to diagnosis of pertussis. In other studied patients levels of specific antibodies did not differ from levels observed in healthy persons and observed clinical signs corresponded to other respiratory diseases. CONCLUSION: Obtained results prove the high incidence of pertussis in adults, its essential importance as etiologic factor of prolonged cough and high informative value of serologic tests.