Method for assessing mucosal immunity state of open cavities of different localisation accompanying prediction of clinical course of infectious-inflammatory processes, and method for correcting infectious-inflammatory processes

FIELD: medicine.

SUBSTANCE: invention represents a method for assessing the mucosal immunity state of open cavities accompanying the prediction of the clinical course of infectious-inflammatory processes, characterised by the fact that having a pathogenetic factor established, degrees of microbiocoenosis disturbances of a specific biotope are recorded with the use of a complex of methods for estimating colonisation resistance factors, namely normal microflora, opportunistic microflora, immunoglobulins G, M, A, secretory immunoglobulin A and sc component; the mucosal immunity state is assessed according to the degree of microbiocoenosis disturbance, and the favourable outcome implying agent eradication or chronisation with agent persistence is predicted. The invention also refers to a method for correcting the infectious-inflammatory processes with the Kipferon® immunomodulator added.

EFFECT: increasing the prediction accuracy of the clinical course of the disease, extending the range of the method for correcting the infectious-inflammatory processes.

2 cl, 3 ex, 6 tbl, 1 dwg

 

The invention relates to the micro-ecology and immunology and can be used to optimize the diagnosis, prognosis and treatment of infectious and inflammatory processes.

Microflora of man is the basis of his microecology and has a direct impact on the livelihoods and status of the microorganism. Microbiocenosis of the open cavities of the microorganism - dynamic microecological system, which components include the macroorganism, its microflora (set of typical for a particular species and specific habitat associations of micro-organisms) and the environment, characterized by the ability to self-regulation, which is an integral part of the body ("additional authority"), the owner and local immunity, in particular, and performs or regulates numerous functions of the microorganism. The indicators of the state of microbiocenosis reflect the reactivity of the microorganism - an organism's ability to respond to the external environment by changing their metabolism, which ensures its adaptation to different habitat conditions. Mucous the open cavities of the microorganism represent a single system. The state of the microbiota and barrier function of the mucous can be assessed according to the severity of colonization resistance (CR) TCI�itih cavities of the body - physiological phenomenon - the ability of the microflora and the host in cooperation to protect the ecosystem of the mucous membranes of pathogens. The CD includes a range of local factors, which include inhibitors of microbial adhesion, biocidal and biostatic products of secrets, the normal microflora, and mechanical factors (ciliated epithelium, the integrity of the skin and mucous membranes), local factors of innate and adaptive immunity. The mechanisms of the phenomenon of CU include the skin and mucous membranes (form a physical and environmental barrier for the penetration of pathological agents into the body), movement of the mucociliary epithelium, gut motility, mucosal desquamation of cells, antimicrobial effect secrets of saliva, bile, gastric and intestinal contents, the composition and quantity of mucin, the tension of oxygen on the thickness of the biofilm, pH of the medium, the update rate of the mucosal epithelium[1, 2, 3, 4, 5].

Currently accumulated a large amount of information about the role of qualitative and quantitative changes in the microflora of the open cavities of the human body in the development of infectious-inflammatory processes.

Thus, the start of most of bronchopulmonary diseases associated with the development of pathological processes in the mucosa of the upper respiratory tract and the oropharynx, which in �Ormes delays and eliminates about 70% coming from outside inert and aggressive antigenic material. Initiation of any infectious inflammatory process depends on the ratio of the levels of indigenous and pathogenic microorganisms that form the biotope. (6, 7). Quantitative and qualitative disturbances in the composition of microbial symbionts gingival fluid, violations of their interaction with the microorganism cause the development of periodontal disease (8).

The causative agents of urogenital chlamydia and ureaplasmosis - obligate intracellular parasites that are not pathogens, but amid growing urbanization, deterioration of the socio-demographic and environmental situations that can cause various complications, adverse effects on General health and reproductive function. Their pathogenic potential depends on the concentration in the organism, the presence or absence of specific genes of pathogenicity, the state of microbiocenosis of the biotope, the Association with other pathogenic bacteria and viruses, changes in physiological and immune status. (9, 10).

Unfortunately, to date the majority of microecological studies were conducted without taking into account local factors and organism resistance. However, the formation of CU mucous membranes, for infectious and inflammatory reactions respiratornog, urogenital and gastrointestinal tracts and is defined as�digenea microflora, and local factors of immune protection.

The known method of assessment of biocenosis of the genital tract in female patients, consisting in the determination of lysozyme activity of the vagina, the pH of the vaginal flora with microbial count the total number (by culture on blood agar) (patent RU №2179849, 2002.02.27, A61K 31/19, 35/74).

The disadvantages of this method are:

- the impossibility to conduct a comprehensive assessment of the state of microbiocenosis of the vagina with regard to the quantitative indicators of the content of facultative anaerobic and obligately-anaerobic microflora in the discharge and in the scrapings from the vagina in conjunction with the definition of the components of the humoral resistance and barrier function of the mucous membrane of the vagina;

- lack of data in laboratory tests to predict and evaluate the efficacy and stability of correction of the state of microbiocenosis of the vagina.

Known method of estimating the microecology of the vagina in the diagnosis of vaginal infections, which consists in the exclusion of sexually transmitted infections, microscopy of vaginal smears, gram-stained, and sowing vaginal discharge to facultative anaerobic group of microorganisms and microaerophile. On the basis of microbiological criteria for the assessment of microecology of the vagina diagnose normocenosis, bacterial vaginosis, VA�Inal candidiasis, nonspecific vaginitis, cytolytic vaginosis, atrophic colpitis or an intermediate microcenosis (11).

The disadvantages of this method are:

- the impossibility to conduct a comprehensive assessment of the state of microbiocenosis of the vagina while the study of quantitative indicators of the content of facultative anaerobic and obligately-anaerobic microflora in the discharge and in the scrapings from the vagina in conjunction with the definition of the components of the humoral resistance and barrier function of the mucous membrane of the vagina;

- lack of data in laboratory tests to predict and evaluate the efficacy and stability of correction of the state of microbiocenosis of the vagina.

Known method of estimating the microbiocenosis of the uterine cavity in women with endometrial polyps in postmenopausal period by determining the quantitative and qualitative composition of microflora and quantify the impact of local humoral immunity, including the capture sosabravo material from the uterine cavity, the sowing of sosabravo material to identify species of microorganisms pathogenic facultative anaerobic and obligately anaerobic microorganisms and their sensitivity to antibiotics, the introduction into the uterus of a solution reopoliglyukina, the definition in the aspirate concentration of IMM�of noglobulins IgG, IgM, IgA, free, secretory component (sc) and secretory immunoglobulin A (sIgA) by radial immunodiffusion according to Mancini and evaluation of microbiocenosis: normocenosis the uterine cavity on the background of endometrial atrophy in the absence of opportunistic facultative anaerobic and opportunistic obligately-anaerobic microflora and certain concentration of immunoglobulins; violation of microbiocenosis at a certain content of conditionally pathogenic facultative anaerobic and opportunistic obligately-anaerobic microflora and at a certain concentration of immunoglobulins. The above method allows to increase the efficiency of diagnostics (patent RF №2430365).

Known method for the diagnosis of chronic urogenital chlamydiosis (patent RF №2327995), when determining in socalmom material from urethra with the use of polymerase chain reaction in real time the levels of expression of toll-like receptors: TL-receptor-2 and TL-receptor-4 and diagnosed with chronic urogenital chlamydiosis when the expression levels in socalmom material from the urethra TL-receptor-2 not more than 5 units and TL-receptor-4 is not more than 5 units. The levels of expression of TL-receptor-2 and TL-receptor-4 was determined using recommendations for conducting polymerase chain reaction in real time (Abramov, D. D., Trofimov D. Yu., Rebrikov.In. The accuracy of polymerase chain reaction methods "in real time" in determining the content of genetically modified sources in food // Applied biochemistry and Microbiology. - 2006. - Vol. 42, No. 4. - P. 485-488; RU patent 2294532 C1, G01N 21/64).

This method evaluates one of the factors mucosal immunity - innate immunity.

The object of the invention is to develop method for the assessment of mucosal immunity of mucous membranes of the open cavities of different localization in the prediction of the course of infectious and inflammatory processes.

The problem is solved in such a way that when the pathogenic factor register of degrees of violations microbiocenosis particular biotope open mucous cavities of different localization with the use of methods of assessing the levels of factors of colonization resistance as an integrating component of mucosal immunity in smears and socalmom material with mucous membranes (normal microflora, pathogenic microorganisms, neutrophils, cytokines, immunoglobulins IgG, IgM, IgA, sIgA and sc component and TLR-receptors) and depending on the degree of violation of microbiocenosis assess:

- good condition mucosal immunity in second and third degree violation of microbiocenosis and predict a favorable outcome Zab�of is indicated with the eradication of the pathogen;

- impaired mucosal immunity in the normocenosis and first-degree violation of microbiocenosis and predict chronic infectious-inflammatory process with persistence of the pathogen.

Under local (mucosal) immunity refers to the complex cellular and secretory nonspecific reactions, including the barrier function of skin cells and mucous membranes, phagocytic activity of neutrophils and macrophages, T-cell immunity, antibodies, antimicrobial proteins of the external secrets, enzyme inhibitors, cytokines. Local immunity is not identified with secretory immunity, but as its Central element is considered In-cell response of the lymphoid tissue of the mucous membranes involving the glandular epithelium, secretory component supplying. The concept of local immunity currently includes the aggregate response of all cells of the lymphoid series that populate the mucous membranes, in cooperation with macrophages, neutrophilic and eosinophilic granulocytes, mast cells and other cells of connective tissue and epithelium[3, 12, 13, 14, 15, 16, 17]. Consequently, the microbial associations of the mucous of the open cavities and mucosal immunity can be regarded as an integral structural-functional system of the body.

In connection with viescas�tion and on the basis of the conducted comprehensive research seems relevant to identify the relationship of the characteristics of microbiocenosis factors and mucosal immunity of mucous membranes of the open cavities of different localization in normal and infectious diseases.

Any infectious process in the mucosa, regardless of etiology, is developing according to the same scenario. The first step is the adhesion of microbes in the parietal mucin or epithelial cells, which are protected by special structures of the pathogen. Once established, the organisms begin to multiply, leading to pathological colonization of the mucosa is the second stage of the infectious process (dysbiosis). Next, the third stage of infection is the invasion of microorganisms, when they overcome the protective mucosal barrier and penetrate the epithelial cells or underlying tissue, causing local immune response (colitis, vaginitis, pharyngitis, etc.). Overcoming local protective barrier possible generalization of infection. Pathogenicity of certain types of bacteria depends on the presence or absence of members of other species. Therefore, the assessment of microbiocenosis of the mucous need to consider the number and species composition of microorganisms, freely located in the lumen and adhered to the epithelial surfaces (parietal region).

It is known that the system of anti-infective resistance of the organism is determined by the qualitative and quantitative composition of the biofilm formed by indigenoustribal, and pathogens to epithelial surfaces, and local anti-infective organism resistantly owner. The key element in the recognition of a microorganism pathogens are TL-receptors (TLR) that form the basis of membrane complexes and is expressed on all the cellular elements involved in the development of resistance (including CU of microorganism), including on mucosal surfaces.

TLR can recognize a conservative molecular structure, common among a certain class of micro-organisms and absent in humans. Anti-infective protection at the local level develops through the formation of a typical inflammatory response after interaction of pathogens with TLR that is followed by the activation of genes in the cytokine cascade responsible for the activation of phagocytes and other immune cells, Ig, which, in turn, determines the level of mucosal CU and, further, the blocking activity, disintegration and destruction of the infectious agent from the body.

So, us in the study of urogenital chlamydiosis and anaplasmosis, an acute infectious disease of the upper respiratory tract, including acute and chronic bronchitis, a link was established toll-like receptor - TLR (launch control cytokine cascade IU�a combined anti-infective resistance, through which runs the immunoglobulin level and inflammatory reaction) with the microflora of the biotope, which determines the colonization resistance of the mucous membranes, characterizing the infectious process, the severity of the clinical and laboratory manifestations and disease outcome (cure, chronic). Colonization resistente as an integral part of mucosal immunity.

The function of TLR was evaluated original patented method of determining the level of gene expression (TLR) polymerase chain reaction (PCR) real-time reverse transcription using specific primers (RU patent 2294532). It is established that pathogens and opportunistic pathogens (UPM), when applied to mucous membranes of the open cavities interact with TLR epithelial cells and run through the activation of the cytokine system inflammatory response. TLR-2 and TLR-4 are reacting to a bacterial pathogen, a TLR-3 and TLR-8 - viral. In the interaction of the pathogen with sensitive cellular elements of the mucous TLR cells respond the expression of genes in the pathogen and UPM, and in the interaction of the pathogen with insensitive for him by the epithelial cells of the mucous - only at UPM. In acute and chronic infectious processes leading etiological factors of the infectious process and are�Association of bacterial and viral pathogens, and PBSO. Different levels of activation of gene expression of TLR-2, TLR-4, TLR-3, TLR-8 depend on the qualitative composition of microbial communities (in particular the predominance of gram-positive or gram-negative pathogens or viral pathogens) present in the mucous membranes of the open cavities of the body. Activation of gene expression of TLR-2, TLR-4, TLR-3, TLR-8 expression occurs more in response to pathogens and PBSO and less than the expression on normalor. Levels of contamination UPM directly correlate with the levels of gene expression of TLR-2, TLR-4, TLR-3, TLR-8. The levels of gene expression of TLR-2, TLR-4, TLR-3, TLR-8 are the criteria for assessing the severity of inflammatory processes. Increasing the gene expression of TLR-2, TLR-4, TLR-3, TLR-8 correlates with the severity of clinical manifestations, and with the recovery of their decline indicates eradication of the pathogen. Natural or acquired suppression of genes TLR-2, TLR-4, TLR-3, TLR-8 leads to chronic infection. In acute infectious process, the detection of low levels of TLR-2, TLR-4, TLR-3, TLR-8 indicates the start of the chronicity of the infection process. The proposed method of assessing TLR can be considered as additional lab test, clarifying the clinical picture and the prediction outcome of the disease.

Infectious lesions of the open cavities of the body generic and species composition MICR�organisms pathogens and UPM, isolated from patients, can serve as an additional objective criterion of the severity of the infectious process, and allows differentiation to judge the effectiveness of antibiotic therapy and make adjustments as necessary. Acute infectious process is accompanied by a significant decrease in levels of indigenous microflora in luminal parietal and habitats of mucous, increased their colonization UPM, a multiple increase in the levels of gene expression of TLR-2, TLR-4, TLR-3, TLR-8, cytokines IL-1β, IL-8, INF-γ, TNF-α, immunoglobulins IgG, IgA, sIgA, IgM and SC and the severity of the local inflammatory response (found a significant correlation between changes in the levels of these factors), indicating a good local anti-infective resistance. Chronic infectious process, compared with the acute course, accompanied with exacerbation less pronounced significant decrease in levels of indigenous microflora in luminal parietal and habitats of the mucous membranes, increasing UPM, increasing levels of gene expression of TLR-2, TLR-4, TLR-3, TLR-8, cytokines IL-1β, IL-8, INF-γ, TNF-α, immunoglobulins IgG, IgA, sIgA, IgM and SC and mild local inflammatory reaction, indicating the violation and the reduction of mucosal anti-infective resistance.

Considering p�iudenich above information and regulations for assessment of colonization resistenti mucous open body cavities was proposed original methodology for evaluation of disorders of microbiocenosis.

Assessment of severity of disorders of vaginal microbiocenosis (PL.1):

- normocenosis vagina (VL) is determined when the presence on the surface of less than 25 epithelial cells bacterial cells, gram-positive rods, with the number of cells less than 10 in the field of view, in the absence of clue cells (I, the purity of the stroke), when the content in the detachable 6-8 lg CFU/g lactobacilli, when the content in socalmom material 7-10 lg CFU/g lactobacilli, in the absence of detachable and socalmom material opportunistic facultative anaerobic and obligately-anaerobic microflora and when the concentration in the flush of IgA 0 μg/ml, sIgA ≤10 µg/ml, IgM 0 µg/ml, SC ≤10 µg/ml;

- intermediate type of microbiocenosis of VL in the presence on the surface of epithelial cells 25-50 bacterial cells, gram-positive Bacillus, isolated gram-positive cocci and gram-negative rods, with the number of cells 10-20 in the field of view, in the absence of clue cells (II degree of purity of the stroke), when the content in the detachable 4-5 lg CFU/g lactobacilli, 3-4 lg CFU/g pathogenic facultative anaerobic or obligately-anaerobic microflora and/or when the content in socalmom material 5-6 lg CFU/g lactobacilli, 1-2 lg CFU/g pathogenic facultative anaerobic or obligately-anaerobic microflora and when the concentration in your chants�e IgA≤10 µg/ml sIgA 11-15 µg/ml, IgM≤10 µg/ml, SC 10-25 µg/ml;

- dysbiosis VL in the presence on the surface of 50-100 epithelial cells bacterial cells, gram-positive rods, gram positive cocci and gram-negative rods, with the number of cells 20-40 in sight, in the presence of clue cells in less than 5 field of view (III degree of purity of the stroke), when the content in the detachable 1-3 lg CFU/g lactobacilli, 5-7 lg CFU/g pathogenic facultative anaerobic microflora and 3-4 lg CFU/g pathogenic obligately-anaerobic microflora and/or when the content in socalmom material 3-4 lg CFU/g lactobacilli, 3-4 lg CFU/g pathogenic facultative anaerobic microflora and 5-7 lg CFU/g pathogenic obligately-anaerobic microflora and when the concentration in the flush of IgA 11-15 µg/ml sIgA 16-30 ug/ml, IgM 11-20 µg/ml, SC 26-50 mg/ml;

bacterial vaginitis in the presence on the surface of epithelial cells is not less than 100 bacterial cells, isolated gram-positive rods and abundant gram-negative and gram-positive rod and coccal flora, with the number of cells at least 40 in sight, when the number of key cells in at least 5 field of view (IV degree of purity smear), in the absence in the discharge of lactobacilli, when the content in the detachable 5-6 lg CFU/g monocultures opportunistic optional-anaa�obnoy or obligately-anaerobic microflora and/or when the content in socalmom material 1-3 lg CFU/g lactobacilli, 6-8 lg CFU/g monocultures opportunistic facultative anaerobic or obligately-anaerobic microflora and when the concentration in the flush of IgA>15 µg/ml sIgA>30 mcg/ml, IgM>20 µg/ml, SC>50 μg/ml.

Assessing the severity of violations microbiocenosis of the cervical canal (PL. 2):

- normocenosis microbiocenosis of the cervical canal (CC) is determined when the number of white blood cells<4 in sight, when the content in socalmom material 1-2 lg CFU/g PBSO and when the concentration in the flushing IgG≤8 µg/g protein, sIgA≤7 µg/g protein, SC≤8 µg/g protein;

- intermediate type of microbiocenosis of the Central Committee is determined when the number of leukocytes 8-10 in sight, when the content in socalmom material 2-3 lg CFU/g PBSO and when the concentration in the flushing IgG 10-13 mg/g protein, sIgA 11-14 µg/g protein, 13-19 SC µg/g protein;

- dysbiosis microbiocenosis of the Central Committee is determined with the number of cells 14-40 in sight, when the content in socalmom material 3-4 lg CFU/g PBSO and when the concentration in the flushing IgG 30-40 mcg/g protein, sIgA 20-30 mcg/g protein, SC 30-40 mcg/g protein;

bacterial vaginitis microbiocenosis of the Central Committee is determined when the number of leukocytes >40 in sight, when the content in socalmom material >4 lg CFU/g PBSO and when the concentration in the flushing IgG>40 mg/g protein, sIgA>30 mcg/g protein, SC>40 mg/g protein.

Estimation expressed�spine of microbiocenosis of the oropharynx (table. 3):

- normocenosis, characterized by the absence of microecological disorders, the presence of indigenous microflora: Streptococcus spp. in the amount of 5-6 lg CFU/g, Neisseria spp.- 4-6 lg CFU/g at the concentration of IgA in saliva<20 mcg/ml sIgA<20 mcg/ml, IgM 0 μg/ml, IgG<50 µg/ml, SC<50 µg/ml;

- an intermediate type (I) the extent of dysbiotic disorders) characterized by the growth of normal flora {Streptococcus spp. 6-7 lg CFU/g, Neisseria spp.- 6-7 lg CFU/g) and the emergence of UPM in up to 3-4 lg CFU/g at the concentration of IgA in saliva 20-50 mcg/ml sIgA 20-50 μg/ml, IgM<10 µg/ml, IgG 50-100 µg/ml, SC 50-100 µg/ml;

- dysbiosis (II degree of dysbiotic violations) of the oropharynx, in which there is an increase in the number of normal flora {Streptococcus spp. 6-7 lg CFU/g, Neisseria spp.- 6-7 lg CFU/g), increasing the level of facultative anaerobic UPM to 4-5 lg CFU/ml, the emergence of virulent variants UPM characterized by severe pathogenicity factors, when the concentration of IgA in saliva 50-100 mcg/ml sIgA 50-100 μg/ml, IgM 10-30 μg/ml, IgG 100-200 µg/ml, SC 100-200 μg/ml;

- acute inflammatory process (grade III dysbiotic violations), characterized by a significant increase in the content of Streptococcus spp. 7-8 lg CFU/g, Neisseria spp.- 7-8 lg CFU/g, PBSO and the number of virulent microorganisms to 6-8 lg CFU/ml when the concentration of IgA in saliva>100 µg/ml sIgA>100 µg/ml, IgM>30 mcg/ml, IgG>200 µg/ml, SC>200 µg/ml.

Assessment �imagenote of intestinal microbiocenosis (PL.4):

- normocenosis: content of E. coli ≥8 lg CFU/g, Lactobacillus ≥7 lg CFU/g of bifidobacteria ≥9 lg CFU/g, no UPM when the content in coprofiltrates IgA <10 mcg/ml sIgA <10 µg/ml, IgM 0 μg/ml, IgG <10 µg/ml, SC <10 µg/ml;

- I degree of intestinal dysbiosis is characterised by increased or reduced content of Escherichia coli (≥ or ≤8 lg CFU/g), a decrease of lactobacilli (≤6 lg CFU/g) and Bifidobacterium (≤9 lg CFU/g) when the content in coprofiltrates IgA ≤10 µg/ml sIgA ≤10 µg/ml, IgM ≤5 µg/ml, IgG 10-20 µg/ml, SC≤10 µg/ml;

- II degree of intestinal dysbiosis characterized by a reduced content of Escherichia coli (≤8 lg CFU/g), Lactobacillus (≤6 lg CFU/g) and Bifidobacterium (≤8 lg CFU/g), the emergence of UPM in the number of ≥4 lg CFU/g, when the content in coprofiltrates IgA 10-20 mcg/ml sIgA 10-20 µg/ml, IgM 5-10 µg/ml, IgG 20-40 µg/ml, SC 10-20 mcg/ml;

- Ill the degree of intestinal dysbiosis characterized by a significant decrease in the content of Escherichia coli with unmodified enzymatic properties (≤6 lg CFU/g), the emergence of suboperations and/or hemosiderosis Escherichia coli (≥4 lg CFU/g), high content lactosonegative enterobacteria, gram-negative glucose non-fermentative bacteria, coccal flora (≥6 lg CFU/g), a sharp decrease in the content of lactobacilli and bifidobacteria ≤5 lg CFU/g and ≤7 lg CFU/g, respectively, with�Ergani in coprofiltrates IgA > 20 ug/ml sIgA >20 µg/ml, IgM >10 µg/ml, IgG >40 µg/ml, SC >20 µg/ml.

The following examples show the use of the inventive method for the assessment of muzealnego immunity of mucous membranes of the open cavities of different localization in the prediction of the course of infectious and inflammatory processes.

Example 1.

We examined 30 healthy children and 77 children with acute and recurrent diseases of the respiratory tract at the age of 3-14 years. The children were divided into 3 groups: group 1 - control group (30 healthy children), group 2 - patients with acute bronchitis (51 children), group 3 - patients with chronic bronchitis (15). The frequency of infection with adenovirus was significantly higher in acute bronchitis versus chronic bronchitis and clinically healthy patients. Differences in colonization of the mucosa of the posterior pharyngeal wall by indigenous microorganisms in the control group and patients with bronchitis children is not valid as quantitative content and frequency of occurrence, however, a sick child, they exceeded the indicators of normocenosis (PL.5). This indicates a compensated form of dysbiotic disorders in the upper respiratory tract. Significant differences in frequency of infection for S. aureus and Candida in acute bronchitis along with�avanyu with chronic bronchitis and clinically healthy patients. The intensity of colonization of the posterior pharyngeal wall by opportunistic microorganisms (OM) were significantly higher in acute bronchitis, and chronic bronchitis changes are not significant compared with healthy patients. Detection in saliva elevated levels of total IgE in acute and chronic bronchitis suggests active and quantitative increase in infectious component. In clinically healthy children normocenosis was observed in 48.1% of patients, intermediate type in 44.4%, dysbiosis - in 7.4% of patients that differed significantly from those of acute bronchitis: normocenosis - 21.6% of patients (p<0.05, and an intermediate type - 11.8% of patients (p<0.01, dysbiosis - in 35.3% of patients (p<0,05, acute inflammatory process - in 31.4% of patients (p<0.01; in chronic bronchitis the normocenosis - 20,0% patients at p<0.05, and an intermediate type - 20,0% of patients (p<0.01, diarios in 33.3% of patients (p<0,05, acute inflammatory process - in 26.7% of patients (p<0.01; significant differences between acute and chronic bronchitis have not been identified. Therefore, in acute bronchitis violations microbiocenosis mucous observed dysbiosis and a strong inflammatory process. However, high levels of normal flora in combination with high levels of Ig provide expressed CU, which is confirmed by high results�s index natural colonization nasopharyngeal epithelium (ACNE). Inoculation UPM in the titer of 6 Ig CFU/g and above may indicate the acquisition of phenotypic markers of virulence.

Notes: ACNE - index natural colonization of the nasopharyngeal epithelium.

In acute bronchitis, in response to an expressed bacterial-viral investigated the impact of TLR reacted reliable five-fold increase in gene expression compared with chronic bronchitis and the control group. Moreover, the apparent specialization TLR: TLR-2 and TLR-4 reacted mainly on bacterial pathogens and TLR-3 and TLR-8 - viral pathogens. The highest values of gene expression occurred during mixed infections, due, to some extent, cross-action of ligands. In chronic bronchitis the levels of expression of TLR genes mostly did not differ from the control group.

In acute bronchitis, in response to a significantly high infection burden (in the form of extincti viral pathogens and UPM) raise the levels of gene expression of TLR-2, TLR-4, TLR-3 and TLR-8 that starts in the upper respiratory tract the production of proinflammatory cytokines IL-8, TNF-α and IL-1β, leading, in turn, increase levels of immunoglobulins that can be regarded as a pronounced local inflammatory immune response of an organism reflect�th acute infectious process and contributing to the localization of the infectious process, and to stimulate the production of additional cytokines neighboring uninfected cells. In the oropharynx increase levels of immunoglobulins sIgA and sc due to their synthesis in situ. The TLR expression levels directly correlate with the levels of sIgA and lysozyme, showing their relationships as components of colonization resistance, reflecting the state of innate immunity, and do not correlate with higher rates of index ACNE indicating a low adhesive capacity of the epithelium of the oropharynx regarding PBSO. All together indicates a high level of colonization resistance as an indicator of mucosal immunity. There is no connection between TLR and IgE. In chronic bronchitis, in response to weak infectious burden (in the form of extincti viral pathogens and UPM) levels of gene expression of TLR-2, TLR-4, TLR-3, TLR-8 are not increased; not detected a direct correlation with reduced, compared with those in acute bronchitis, the levels of cytokines, IgM, sIgA; logged chronic, indolent inflammatory process. The levels of expression of TLR practically does not directly correlate with the levels of sIgA and lysozyme; correlate with higher rates of index ACNE that can improve adhesion UPM on the skin cells. All together makes �the violation of colonization resistance as an indicator of mucosal immunity, contributes to the progressive nature of the flow of infection and imbalance in the processes of destruction and reparations-related inflammation. There is no connection between TLR and IgE.

In acute and chronic bronchitis the relationship of receptors of innate immunity TLR-2, TLR-4, TLR-3, TLR-8 (launch control cytokine cascade, local anti-infective resistance, through which runs the immunoglobulin level and inflammatory reaction) with germline biotope CU determines the mucous membranes, characterized by an infectious process, the severity of the clinical and laboratory manifestations and disease outcome (cure, chronic). We found a significant relationship TLR with other factors of innate immunity lysozyme, ACNE, sIgA and sc. The levels of IgE-independent TLR. A fivefold increase in the levels of gene expression of TLR-2, TLR-4, TLR-3, TLR-8 and cytokines IL-1β, IL-8, INF-γ, TNF-α, suggesting a good local anti-infective resistance, and lack of improvement indicates its violation and chronic disease (is of diagnostic and prognostic character).

A significant increase in median gene expression TLR-2 was detected only in acute bronchitis, and mixed infection compared to chronic bronchitis and control� group at p< 0,0001. The median gene expression TLR-4 in acute bronchitis were significantly lower during infection UPM in comparison with chronic bronchitis (p<0,0001), significantly higher in the mixed infections in comparison with chronic bronchitis and the control group (p<0,0001), while no infection was significantly higher in the control group compared with chronic bronchitis (p=0,007).

The median gene expression TLR-3 in acute bronchitis were significantly higher in comparison with chronic bronchitis (p < 0,006) during infection by viral pathogens and mixed infections (p<0,0001). The median gene expression TLR-8 in acute bronchitis were significantly higher in comparison with chronic bronchitis (p < 0,006) mixed infection (p<0,0001); in chronic bronchitis it is higher than that in acute bronchitis infection with viral pathogens (p<0,0001) and without infection were significantly higher compared with the control group (p=0.001). Therefore, in acute bronchitis, in response to an expressed bacterial-viral investigated the impact of TLR reacted reliable increase of gene expression compared with chronic bronchitis and the control group. Moreover, the apparent specialization TLR:

TLR-2 and TLR-4 reacted mainly on bacterial pathogens and TLR-3 and TLR-8 - viral pathogens. The highest values of gene expression occurred during mixed infection, �that explains to some extent, cross-action of ligands. In chronic bronchitis the levels of expression of TLR genes mostly did not differ from the control group (Tab.6.)

Thus, when verified pathogenetically agent third degree violations microbiocenosis of the oropharynx - acute inflammatory process reflects a pronounced inflammatory response with bronchitis and demonstrates the usefulness of mucosal immunity; second degree violations microbiocenosis of the oropharynx - the biocenosis is intermediate between the first and third degrees and indicates a normally occurring reaction mucosal immunity; first degree violations microbiocenosis of the oropharynx - intermediate type indicates disturbances in mucosal immunity.

Example 2.

Clinical-anamnestic and laboratory data of 228 patients with urogenital chlamydiosis (ugh) allowed to select 100 patients who were divided into 3 groups. Group I was 41, the patient is initially infected patients in the acute stage of the infection process. Group II consisted of 29 patients with a chronic course of chlamydia infection. In III (control group) included 30 patients - previously had (long ago moved chlamydial infection). The control group consisted of 32 healthy women (group IV, the control group compared�termination).

UPM vagina (VL) in acute urogenital chlamydia (ugh) was determined in the amount of 8.1±0,4 lg CFU/ml, at exacerbation of chronic ugh - 4,6±1,0 lg CFU/ml, I had been ill - 2,5±1,2 lg CFU/ml, in healthy patients - to 2.74±0,94 lg CFU/ml. Levels identify UPM in acute ugh differed (p<0.05) from those found in other comparable groups of patients. The frequency of detectable™ UPM in OTL revealed significant differences between I and II (p<0.01), I and III (p<0,001), I and IV (p<0,001), II and III (p<0.01), II and IV (p<0,001), III and IV groups (p<0.01), and between groups I and II the differences are not significant. Than pronounced pathological process, the wider spectrum of microorganisms and in higher titers they are sown. Indirect evidence of the acquisition of pathogenic properties of the UPM could be the allocation of Overhead strains of obligate anaerobes in acute ugh in titer 7 lg CFU/g, and at exacerbation of chronic ugh in titer 5 lg CFU/g In group I at 43.9% of the patients was diagnosed with bacterial vaginitis and 56,1% - dysbiosis, in group II, 27.5% of women with bacterial vaginitis and 72,4% - dysbiosis, III and IV group of patients-normocenosis. PBSO in the cervical canal (CC) in group I was determined in the amount of 3.70±1,56 lg CFU/ml, in group II - 3,80±0,27 lg CFU/ml, in group III - 1,36±0,37 lg CFU/ml, in group IV - 1,94±0,73 lg CFU/ml According to the frequency of the detection of UPM in the CT differences were found between I and III (p<0.01), I and IV (p<0.001), II and IV (p<0,001), III and IV (p<0.01) groups�, and between I and II, II and III groups the differences are not significant. In group I have to 19.51% of the patients were recorded bacterial cervicitis and 80,48% - dysbiosis, in group II at 13,79% of patients - bacterial cervicitis, 51,7% - dysbiosis and 34,48% - intermediate, III and IV group of patients - normocenosis. Indirect evidence of the acquisition of pathogenic properties of the UPM may be the selection from the CC strains of obligate anaerobes in titer 4 lg CFU/g UPM in the urethra (Ur) in group I is determined by a number 4,20±0,51 lg CFU/ml, in group II - 2,3±0,5 lg CFU/ml, in group III - 2,50±0,83 lg CFU/ml, in group IV - 1,32±0,37 lg CFU/ml. frequency of detection in UPM Ur significant differences found between I and IV (p<0,001), II and III (p<0.01), II and IV groups (p<0,001), and between groups I and II, I and III, III and IV, the differences are not significant. Indirect evidence of the acquisition of pathogenic properties of the UPM may be the selection from Ur strains of facultative anaerobes or obligate anaerobes in titer 4 lg CFU/g.

If yrx levels of contamination UPM CC, Ur and VL directly correlate with the levels of gene expression of TLR-2 and TLR-4. Increasing the gene expression of TLR-2 and TLR-4, as in the CC and Ur, correlates with the severity of clinical manifestations, depending on the chlamydia and associated (pathogens and sexually transmitted infections - STIs, and UPM). In OTL the expression of the gene for TLR-2 and TLR-4 in response to PBSO, and in the CC & RM - �and PBSO and STI pathogens. Activation of gene expression of TLR-2 and TLR-4 expression occurs more in response to UPM and less expression in contact with normoflory. The first set defines the role of TLR-2 and TLR-4 mucous of ATM in the response of host to infection with chlamydia and PBSO if yrx. The levels of gene expression of TLR-2 and TLR-4 are the evaluation criteria of severity ugh and the presence of inflammatory process in patients, and with the recovery of their decline may indicate eradication of the pathogen. If yrx detection in socalmom material from Ur levels of gene expression of TLR-2 more 14 TH and TLR-4 more than 10 OE, and in socalmom the material of the Central Committee of TLR-2 over 19 TH and TLR-4 over 14 TH indicates acute ugh;

identifying socalmom material from Ur levels of gene expression of TLR-2 not more than 5 OE and TLR-4 is not more than 5 OE, and in socalmom the material of the Central Committee of TLR-2 not more than 6 TH and TLR-4 9 TH indicates chronic yrx or the beginning of a chronic infectious process. Similar changes of indicators of the level of expression of TLR-2 and TLR-4 in the CC and Ur patients with chronic chlamydia indicate the development of the phenomenon of receptor depression, accompanied by an imbalance between the development of infection and inflammatory response. Increasing the level of mRNA expression of TLR-2 and TLR-4 and activity in the local synthesis of cytokines in response to chlamydial infection contributes to the favorable outcome of the disease�evania, and low levels are a poor prognostic sign.

In acute chlamydia in response to a high infectious load (chlamydia in the form of mono - or extincti with STI pathogens and/or PBSO) raise the levels of gene expression of TLR-2, TLR-4, launching in the Central Committee expressed the production of IL-8, TNF-α and IL-1β, leading, in turn, increase levels of leukocytes, protein and Ig in patients that can be regarded as a pronounced local (predominantly on the cell type) immunological reaction of an organism reflecting the severity of the infectious process and contributing to the development of the inflammatory response and containment of spread beyond the cervix and stimulate production of additional cytokines neighboring uninfected cells. For chronic chlamydia combination of reduced gene expression of TLR-2 and TLR-4 inhibition activity in the local synthesis of IL-8, IL-6, TNF-α, is relatively weak leukocyte reaction, low levels of sIgA and sc, a high content of total protein and IgG, causes chronic, indolent inflammatory process that contributes to the progressive nature of the flow of the infectious process and indicate a dysfunction of the mechanisms of mucosal immunity of the Central Committee, the imbalance in the processes of destruction and reparations-related inflammation.

So�m, when verified pathogenetically agent third degree violations microbiocenosis of the mucous membranes of the urogenital tract - expressed bacterial vaginitis (bacterial cervicitis) reflects a pronounced inflammatory response to urogenital chlamydia and demonstrates the usefulness of mucosal immunity; second degree violations microbiocenosis of the oropharynx - the biocenosis is intermediate between the first and third degrees and indicates a normally occurring reaction mucosal immunity; first degree violations microbiocenosis of the oropharynx - intermediate type or normocenosis indicates disturbances in mucosal immunity.

The next task of the invention is to provide a method of correction of infectious inflammatory process, considering the state of mucosal immunity and prognosis of infectious-inflammatory process.

A method of treating infectious diseases (patent RF №2146531), including the use of antibiotics and immunomodulators, characterized in that the low titer of specific antibodies in the blood and having regard antibodies to classes of immunoglobulins in subacute, erased, inoperante, slow or chronic course of infection every day or used immunomodulating funds in combination with oral and/or� rectal doses of Bifidumbacterin and/or Azilect, then, when you increase the titer of antibodies in the blood and having regard antibodies to classes of immunoglobulins prescribed for 5 to 14 days of antibiotic therapy and at the end of treatment re-applied immunomodulatory means in combination with oral and/or rectal doses of Bifidumbacterin and/or Azilect.

The disadvantages of this method are that when prescribing this therapy take into account only the titers of specific antibodies in the blood with regard antibodies to classes of immunoglobulins in subacute, erased, inoperante, slow or chronic infections.

The problem is solved in such a way that patients with good condition mucosal immunity determined in accordance with the stated method for the assessment of mucosal immunity and taking into account the prognosis of infectious-inflammatory process in the mucous of different localization prescribe corrective therapy with conventional antibacterial agents with connection immunomodulator until the curing and disappearance of the inflammatory response, and patients with impaired mucosal immunity after the first course of treatments mentioned again in a month to appoint a second similar course of therapy until the curing and disappearance of the inflammatory response.

The following examples �utverjdayut the effectiveness of the proposed method of correction of infectious inflammatory process, considering the state of mucosal immunity and prognosis of infectious-inflammatory process.

Example 1. In children with acute and chronic bronchitis verified pathogenetic Association of adenoviruses, S. aureus and fungi Candida. Thus in acute and chronic bronchitis (acute stage), compared with healthy patients, significantly more frequently with the same frequency of the second (dysbiosis - in to 35.3% and 33.3% of cases, respectively) and the third (pronounced inflammation is at 31.4% and 26.7% of cases, respectively) disbacteriosis of the oropharynx; however, in acute bronchitis versus chronic bronchitis revealed higher levels of indicators of gene expression of receptors of innate immunity TLR and inflammatory responses, all of which indicated a high level of mucosal immunity, the most marked case of acute bronchitis. This was confirmed by the effectiveness of a course of treatment using conventional antibiotic therapy with connection immunobiological drug Kippered®: reducing rates of contamination with viral pathogens, S. aureus and grimmy Candida and the absence of relapse within half a year (observation period) in patients with acute bronchitis, and patients with chronic bronchitis a month after the first course of therapy was required for a run rate to achieve the specified effect. At the same BP�bedrooms in acute and chronic bronchitis in patients with normocenosis - at 21.6% and 20.0% of cases, respectively) and the first (intermediate type - 11.8% and 20.0% of cases, respectively) degrees of dysbiosis fauces, accompanied by significantly lower levels of indicators of gene expression of receptors of innate immunity TLR and inflammatory responses indicating a violation of mucosal immunity, it took repeated use of therapy a month after the first to achieve a therapeutic effect - the decrease of contamination of viral pathogens, S. aureus and Candida and the absence of recurrence after six months; 11.8% of patients with acute bronchitis and 66.7% patients with chronic bronchitis six months later relapse of the disease. In all cases, the recovery was accompanied by a decrease in the expression levels of TLR genes and severity of the inflammatory response in the mucous membrane; the preservation of expressed TLR gene expression and inflammatory response after the first course of treatment demanded its repetition.

Example 2. In acute and chronic (in the acute stage) urogenital chlamydia (ugh) in patients in the cervical canal verified pathogenetic Association of chlamydia, the causative agents of sexually transmitted infections (STIs) and opportunistic microflora (PBSO). Thus in acute and chronic ugh, compared with clinically healthy patient�mi, significantly more frequently with the same frequency of the second (dysbiosis - of 80.5% and 51.7% of cases, respectively) and third (cervicitis - 19.5% and 13.8% of cases, respectively) disbacteriosis urogenital tract (OGC); however, in acute ugh in comparison with chronic ugh revealed higher levels of indicators of receptors of innate immunity TLR and inflammatory responses, all of which indicated a high level of mucosal immunity, is most marked in acute ugh. This was confirmed by the effectiveness of a course of treatment using conventional antibiotic therapy with connection immunobiological drug Kippered®: the registered eradicate chlamydia and relapse was not recorded for six months (observation period) in patients with acute ugh, and patients with chronic ugh a month after the first course of therapy it took a second course to achieve the specified effect. At the same time in patients with normocenosis (0% and 0% of cases,respectively) and the first (intermediate type of 80.5% and 51.7% of cases, respectively) degrees of dysbiosis UHT, accompanied by significantly lower levels of indicators of gene expression of receptors of innate immunity TLR and inflammatory responses indicating a violation of the mucosal IMMA�of IATA, it took repeated use of therapy a month after the first to achieve a therapeutic effect - eradicate chlamydia and lack of recurrence of the disease after six months; 0% of patients with acute ugh and 60% of patients with chronic ugh six months later showed worsening of the disease. In all cases, the recovery was accompanied by a decrease in the expression levels of TLR genes and severity of the inflammatory response in the mucous membrane; the preservation of expressed TLR gene expression and inflammatory response after the first course of treatment demanded its repetition.

Example 3. In acute anaplasmosis in patients vagina verified pathogenetic Association of Ureaplasma, the causative agents of sexually transmitted infections (STIs) and opportunistic microflora (PBSO). Thus in acute ureplazmu, compared with healthy patients, significantly more frequent second (dysbiosis - in 44.0% of cases) and third (vaginitis - at 46.0% of cases) the degree of dysbiosis vagina; thus, in acute anaplasmosis identified high level indicators of the inflammatory response, which confirmed the high level of mucosal immunity. It also confirmed the effectiveness of a course of treatment using conventional antibiotic therapy with connection immunobiological drug Cipfa�it®: 68,0% of patients with dysbiosis and 88,0%

patients with vaginitis clinical recovery occurred with erraticaly Ureaplasma after the first course of treatment, relapse was not recorded for six months (observation period); 32,0% of patients with dysbiosis and 12,0% with vaginitis a month after the first course of therapy it took a second course to achieve the specified effect. At the same time in patients with normocenosis - in 0% of cases) and the first (intermediate type is 10.5% of cases) degrees of dysbiosis vagina, accompanied reliably, compared with dysbiosis and vaginitis, lower levels of indicators of the inflammatory response and infringement of mucosal immunity, it took repeated use of therapy a month after the first to achieve a therapeutic effect - erraticaly Ureaplasma and absence of recurrence after six months; 68,0% of patients with normocenosis and 76,0% of patients with vaginitis after six months showed worsening of the disease. In all cases, the recovery was accompanied by a decrease in the inflammatory response of the mucous membranes; the preservation of a pronounced inflammatory response after the first course of treatment demanded its repetition.

Thus, scientifically substantiated and confirmed the concept that the interaction of microbiocenosis of the mucous of the open cavities of the microorganism is dynamic in nature,�especial vital for the optimal level of reactivity of the microorganism and its anti-infective resistance. Thus, it is authentically confirmed the role of microorganisms in the teaching of protective systems of an organism during ontogeny. Modifying anti-infective resistance to heterologous pathogens in organismic and local levels is defined by a set of pathogenicity factors of microorganisms, which is an integral pathogenic characteristics of the infectious agents causing, ultimately, prognosis and outcome of the disease.

Enlarged views of the mechanism of formation of the start of the infection process, which is the result of the interaction of microorganisms habitats mucous and infectious diseases with TL-receptors, which expression level correlated with the severity of the indicators of local immunity (secretory immunoglobulins and cytokines). Thus, TLR are the first link in the response of the organism to the pathogen that determines the further development of the infectious disease process. Create a quick and non-specific defense against infections is determined by the ability of TLR to recognize almost all pathogen-associated molecular patterns on pathogens, triggering an infectious process. Violation of the mechanisms of TLR leads to the development of immunopathological processes and affect both the development and outcome of infectious� diseases.

For the first time the algorithm of functioning of the CU open mucous cavities as an integral component of the local anti-infective resistance and mucosal immunity in General. (Fig.1.)

The technical result of the present invention is to provide a method of integrated assessment CU mucous as a method of assessing their mucosal immunity. Registration of indicators of levels of TLR, cytokine and Ig mucous has diagnostic and prognostic value and as a result allows you to use a specific correction scheme in violation of mucosal immunity.

The list of references

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3. Immunobiological preparations, application prospects in Infectology. G. G. Onishchenko, V. A. Aleshkin, S. S. Afanasiev, Vladimir Pospelov (ed.). - M., necr MOH, 2002. - 608 p.

4. Kochenower V. I., Bunyatyan N. D. The normal microbial flora of the female urogenital organs and preparations for its correction. - M.: Publishing house "ACTAEON", 2011. - 72 S.

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1. A method for the assessment of mucosal immunity of mucous membranes of the open cavities of different localization in the prediction of the course of infectious and inflammatory processes, characterized in that when the pathogenic factor register of degrees of violations microbiocenosis particular biotope open mucous cavities of different localization with the use of methods of assessing the levels of factors of colonization resistance as an integrating component of mucosal immunity in smears and socalmom material with mucous, namely normal microflora conditionally pathogenic microflora, immunoglobulin - G, M, A, secretory immunoglobulin A and sc component; and depending on the degree of violation of microbiocenosis assess:
- good condition mucosal immunity in second and third degree hard�tion of microbiocenosis and predict favorable outcome of the disease by eradication of the pathogen;
- impaired mucosal immunity in the normocenosis and first-degree violation of microbiocenosis and predict chronic infectious-inflammatory process with persistence of the pathogen.

2. Method of correction of infectious and inflammatory processes, characterized in that conduct assessment of mucosal immunity of mucous membranes of the open cavities of the method according to claim 1 and assign:
- patients with good condition mucosal immunity course of treatment using conventional antibiotic therapy with connection immunomodulator - Kippered® until the curing and disappearance of the inflammatory response
- patients with impaired mucosal immunity course of treatment using conventional antibiotic therapy with connection immunomodulator - Kippered® and again a month later, a second similar course of therapy until the curing and disappearance of the inflammatory response.



 

Same patents:

FIELD: medicine.

SUBSTANCE: content of calcium and protein in oral liquid is determined before and after physical load, as well as a day after physical load. Recovery of content of calcium ions and protein in oral liquid after physical load to initial values is considered to be a criterion of total recovery of athlete's-volleyball player's organism, with evaluating time interval, required for said process.

EFFECT: invention makes it possible to determine reserve abilities of organism and its adaptability in athletes-volleyball players to physical load.

2 dwg, 4 tbl

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SUBSTANCE: invention relates to the field of veterinary and can be used to diagnose the presence of a pathological effect of iron dextran on the piglets' liver. The essence of the method consists in carrying out the morphological systemic step-by-step analysis of histological liver cuts with the description of its histological structure, measurement of the average quantity of binucleate hepatocytes, apoptotic bodies and cells of the mononuclear-macrophage system. If the complex of pathognomonic morphological changes, including the presence of blood filling of sinus capillaries, oedema of the Disse's space; swelling of the vascular endothelium, granular dystrophy of hepatocytes, increase of the average quantity of cells of the mononuclear-macrophage system, including haemosiderophages by two times and more, as well as an increase of the quantity of binucleate hepatocytes and apoptotic bodies by 2 times and more, the effect of iron dextran on the piglets' liver condition is considered to be pathological.

EFFECT: invention provides an increased accuracy of the post-mortem diagnostics of the presence of a pathological effect of iron dextran on the piglets' liver.

1 tbl

FIELD: medicine.

SUBSTANCE: after thymomegalia has been excluded, tissue specimens of three-day-old mature newborns are studied to evaluate areas of inflammation changes in points in the placental umbilical cord (A), in the foetal placenta (B), in the maternal placenta (C), in extraplacental membranes (D); then thymomegalia is predicted by a discriminant equation: DE=-0.350×A-1.176×B-1.690×C-1.203×D, wherein DE is a discriminator function with a threshold equal to - 15.00. If DE is equal to or more than the threshold, the absence of thymomegalia is predicted; if D is less than the threshold, thymomegalia is predicted, whereas the score is taken at: (A) - 1 point - no inflammation, 2 points - amnionitis, 3 points - leukocytic infiltration in the Wharton's jelly, 4 points - phlebitis, 5 points - arteriitis, 6 points - a combination of two or more areas of inflammation: in blood vessels or in vessels and in the Wharton's jelly, (B) - 1 point - no inflammation, 2 points - chorioamnionitis, 3 points - villusitis, 4 points - vasculitis, 5 points - intervillesitis, 6 points - a combination of two or more areas of inflammation, (C) - 1 point - no inflammation, 2 points - villusitis, 3 points - vasculitis, 4 points - intervillesitis, 5 points - deciduitis, 6 points - a combination of two or more areas of inflammation, (D) - 1 point - no inflammation, 2 points - amnionitis, 3 points - chorioamnionitis, 4 points - deciduitis, 5 points - choriodeciduitis, 6 points - a combination of two or more areas of inflammation.

EFFECT: enabling the prediction of thymomegalia in the three-month-old mature newborns suffered prenatal influenza B complicated by placentitis.

2 ex

FIELD: veterinary medicine.

SUBSTANCE: method consists in determining in the scales of concentration of Mn and/or Cu by the method of atomic-emission spectrometry. The regression equation is calculated, and on the content of Mn and/or Cu in the scales a copper concentration is determined.

EFFECT: method is accurate, atraumatic and non-invasive, simple and easy to use.

3 tbl, 1 ex

FIELD: medicine.

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SUBSTANCE: blood serum fasting adiponectin and leptin concentrations are measured in the morning in the female adolescents diagnosed with oligomenorrhea and obesity. An adiponectin/leptin ratio is derived. If the ratio is 0.6 or less, insulin resistance is stated in the female patients suffering oligomenorrhea and obesity, and the therapy is started with prescribing metformin, an insulin sensitiser. The adiponectin/leptin ratio of more than 0.3 enables diagnosing the absence of insulin resistance and prescribing hormonal contraceptives with drospirenone.

EFFECT: effective treatment of oligomenorrhea and obesity by selecting the adequate treatment taking into account the carbohydrate metabolism status.

1 tbl, 3 ex

FIELD: medicine.

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2 dwg, 2 tbl, 3 ex

FIELD: medicine.

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4 ex

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EFFECT: improved assay method.

3 ex

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12 cl, 3 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: method involves carrying out microscopic examination of blood serum samples taken from femoral vein and cubital vein. Femoral vein sample is taken on injured side. The examination is carried out before and after treatment. The blood serum samples are placed on fat-free glass slide in the amount of 0.01-0.02 ml as drops, dried at 18-30°C for 18-24 h. The set of pathological symptoms becoming larger or not changed after the treatment in comparison to sample taken before treatment, and morphological picture of samples under comparison taken from the cubital vein showing no changes or being changed to worse, the treatment is considered to be effective.

EFFECT: enabled medicamentous treatment evaluation in course of treatment to allow the treatment mode to be changed in due time; avoided surgical intervention (amputation); retained active life-style of aged patients.

4 dwg

FIELD: medicine, clinical toxicology.

SUBSTANCE: at patient's hospitalization one should gather the data of clinical and laboratory values: on the type of chemical substance, patient's age, data of clinical survey and laboratory values: body temperature, the presence or absence of dysphonia, oliguria being below 30 ml/h, hemoglobinuria, erythrocytic hemolysis, exotoxic shock, glucose level in blood, fibrinogen and creatinine concentration in blood serum, general bilirubin, prothrombin index (PTI), Ph-plasma, the state of blood clotting system. The state of every sign should be evaluated in points to be then summed up and at exceeding the sum of points being above "+20" one should predict unfavorable result. At the sum of "-13" prediction should be stated upon as favorable and at "-13" up to "+20" - prediction is considered to be doubtful.

EFFECT: higher accuracy of prediction.

2 ex, 3 tbl

FIELD: medicine, juvenile clinical nephrology.

SUBSTANCE: disease duration in case of obstructive pyelonephritis should be detected by two ways: either by detecting the value of NADPH-diaphorase activity, as the marker of nitroxide synthase activity in different renal department and comparing it to established norm, or by detecting clinico-laboratory values, such as: hemoglobin, leukocytes, eosinophils, urea, beta-lipoproteides, lymphocytes, neutrophils, the level of glomerular filtration, that of canalicular reabsorption, urinary specific weight, daily excretion of oxalates, arterial pressure, and estimating their deviation against average statistical values by taking into account a child's age.

EFFECT: higher efficiency of detection.

7 dwg, 1 ex, 6 tbl

FIELD: medicine, urology.

SUBSTANCE: the present innovation deals with differential diagnostics of prostatic cancer and other prostatic diseases at the stage of primary inspection. The method includes the detection of PCA and calculation of probability coefficient for prostatic cancer (PCC) by the following formula: where e - the foundation of natural logarithm (e=2.718…), PCA - the level of total blood PCA in ng/ml, V - patient's age in years. At PCC value being above 0.2 one should diagnose prostatic cancer and to establish final diagnosis one should perform polyfocal prostatic biopsy. The method enables to increase accuracy of diagnostics at decreased number of unjustified prostatic biopsies.

EFFECT: higher efficiency of diagnostics.

2 ex

FIELD: medicine, biology.

SUBSTANCE: invention relates to nutrient medium used for accumulation of cells for the following cytological and/or immunocytochemical analysis carrying out. Invention relates to medium containing salts NaCl, KCl, anhydrous CaCl2, MgSO4 x 6 H2O, MgCl2 x 6 H2O, Na2HPO4 x 2 H2O, KHPO4, NaHCO3, and also glucose and Henx's solution, 10% albumin solution and polyglucin taken in the ratio 1:1:1. Invention provides enhancing the preservation of cells.

EFFECT: improved an valuable properties of nutrient medium.

3 ex

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