Enzymatic Activity Of Leukocyte Elastase Research Articles

Comparative Characteristics of Inflammatory Markers in Alzheimer’s Disease in Males and Females

Background: the role of the sex factor in the differences between the manifestations of normality and pathology is not limited to the phenomenon of sexual dimorphism. It is known that the prevalence of certain diseases in males and females is different, in particular, there is a multiple increase in the incidence of dementia in females compared to males in Alzheimer’s disease (AD). Taking into account the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, there is reason to assume gender differences in inflammation indicators at different stages of dementia in AD. The aim of the study was to conduct comparative analysis of indicators of the inflammatory system in the blood plasma of males and females at different stages of Alzheimer’s disease. Patients, control group and methods: a total of 210 patients with AD (101 males and 109 females) aged 49 to 94 years (average age 72.3 ± 8.2) with varying degrees of dementia severity, i.e. mild, moderate, severe, were examined. In peripheral blood plasma, the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) were determined by the spectrophotometric method, and the level of C-reactive protein (CRP) and IL-6 were determined by the enzyme-linked immunosorbent method (ELISA). The control group consisted of 52 healthy people, who did not differ from the patients in age and gender. Results and discussion: in the blood of patients with varying severity of dementia in AD, a statistically significant increase in α1-PI activity was observed compared to controls (p < 0.0001), regardless of gender. For all subgroups of patients with AD, the indicators of LE enzymatic activity were within the control range or beyond its lower limit. Low LE activity was observed in males compared to females both in the general group and in moderate dementia (p = 0.005105, p = 0.028672, respectively). In severe dementia, a significant decrease in LE activity compared to the controls did not depend on gender. Low LE activity in the blood of patients with AD, along with elevated levels of other inflammatory markers, may reflect a critical violation of the permeability of the blood-brain barrier and/or functional exhaustion of neutrophils due to a long-term inflammatory process. In males, compared with females, an increase in the level of the pro-inflammatory cytokine IL-6 was detected in the general group and in moderate dementia (p = 0.021238, p = 0.027894, respectively). A highly significant increase in CRP levels was only detected in males in subgroups with different severity of dementia. CRP levels in males were significantly higher than in females at the stage of moderate and severe dementia (p = 0.000906, p = 0.000049, respectively). Conclusion: distinctive features of inflammatory markers spectrum were identified, depending on gender and severity of dementia in AD. These results can be used to develop sex-specific preventive or therapeutic strategies for patients with mild cognitive impairment to determine risk and resistance to developing dementia.

Logistic regression model for the prediction of asthenia development in schizophrenia based on inflammatory blood markers

IntroductionAccording to a number of authors, inflammation is involved in the development of asthenic syndrome in different diseases. The results of our own studies indicate that the main feature of the spectrum of inflammatory markers in patients with asthenic syndrome in schizophrenia is low enzymatic activity of leukocyte elastase against the background of high levels of other inflammatory markers. Presumably, the decrease in LE activity may be associated with functional exhaustion of neutrophils and/or their transmigration to the brain through the disrupted blood-brain barrier due to a long-term chronic inflammatory process.ObjectivesTo create a logistic regression model for predicting the development of asthenia in schizophrenia based on the analysis of the association between leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity in blood plasma.MethodsA database including clinical and demographic parameters (ICD-10 diagnosis, duration of the disease, psychometric evaluation according to the PANSS and MFI-20 scales, sex and age) and immunological parameters (enzymatic activity of LE and functional activity of α1-PI in blood plasma) of 95 patients from 22 to 55 years old with paroxysmal-progressive (F20.x1) and paranoid (F20.00) schizophrenia was used to construct the model. An asthenic symptom complex was diagnosed in 61 patients.ResultsA binary logistic regression model linking the probability of developing asthenia to LE and α1-PI activity was constructed by analyzing a database of patients with schizophrenia.P=1/(1+exp [-(11.71-0.057-LE+0.027-α1-PI)] (2), whereP is the probability of asthenia development; exp is the base of the natural logarithm; 11.71 is the regression constant; 0.057 is the coefficient for LE; 0.027 is the coefficient for α1-PI.This model adequately describes the clinical data and has good predictive ability (sensitivity - 93.44%, specificity - 76.47%, AUC - 0.89).ConclusionsA binary logistic regression model was created to predict the development of asthenia in schizophrenia using immunological parameters LE and α1-PI. The model is highly effective and can complement clinical examination of patients with schizophrenia, contributing to the objective diagnosis of asthenic syndrome and, consequently, timely therapeutic correction.Disclosure of InterestNone Declared

Diagnostics and Assessment of the Severity of Alzheimer’s Disease: Machine Learning Algorithms Based on Markers of Inflammation

Background: as the most common form of dementia, Alzheimer’s disease (AD) is characterized by cognitive deterioration and usually begins with loss of memory of recent events. It is important to search for biological, sensitive and affordable methods that could be used for early diagnostics of AD and determine the severity of the disease.Objective: to develop machine learning algorithms based on such inflammatory markers as the enzymatic activity of leukocyte elastase (LE) and the functional activity of the α1-proteinase inhibitor (α1-PI) for diagnosing and assessing the severity of AD.Patients and methods: the study included128 people aged 55 to 94 years (73.7 ± 7.9 years), of which 91 patients were diagnosed with Alzheimer’s disease and 37 apparently healthy people (control). The indicators of LE and α1-PI in blood plasma were used as classifying features for building models. The following algorithms were used to build a machine learning model: Optimal Valid Partition (OVP), logistic regression (LR), support vector machine (SVM), random forest (RF), gradient boosting (GB) and statistically weighted syndromes (WSWS). The predictive performance of the constructed classiers was evaluated by the overall accuracy (accuracy), sensitivity (sensitivity), specificity (specificity), F-measure and ROC-analysis.Results: the developed machine learning algorithms made it possible to reliably divide the general group of subjects (patients + conditionally healthy), as well as patients with different AD severity, into 4 quadrants of a two-dimensional diagram in the LE and α1-PI coordinates and showed close and fairly high predictive efficiency.Conclusion: the developed machine learning algorithms have proven close and sufficiently high prognostic efficacy for assessing the severity of AD based on inflammatory markers (enzymatic activity of LE and functional activity of α1-PI) and, probably, can be useful for early diagnostics of the disease and timely administration of therapy.

Predicting the Dynamics of Mild Cognitive Impairment According to Immunological Parameters

Background: neuroin flammation is an important link in the pathogenesis of pre-dementia cognitive impairment and the development of dementia in Alzheimer’s disease.The aim of the study was to determine the prognostic value of inflaammatory markers (enzymatic activity of LE and its inhibitor alpha1-PI) at the stage of mild cognitive impairment for subsequent follow-up evaluation.Patients and methods: a total of 103 patients with an amnesic type of mild cognitive impairment (aMCI) aged 50 to 89 years (mean age 68.1 ± 9.4 years) were examined. Mental status of the patients was assessed clinically and by psychometric scales and tests. After 3 years of observation, the patients were divided into two groups depending on the dynamics of cognitive status: the 1st group consisted of 49 patients with progression of cognitive decline to the degree of dementia; the 2nd group included 54 patients with a stable state of cognitive functions. The control group included 61 subjects of the same age and gender. The enzymatic activity of leukocyte elastase (LE) and the functional activity of the α1-proteinase inhibitor (α1-PI) were determined in blood plasma. Cluster analysis was used to isolate immunotypes.Results: the functional activity of α1-PI at the starting point of the study in patients of both follow-up groups exceeded the control values (p = 0.000001, p = 0.000006, respectively). Follow-up groups differed in LE activity at the initial stage. In patients of the 1st group (with an increase in cognitive impairment) LE activity did not differ from the control values (p = 0.144651). Group 2 (with stable cognitive functions) was characterized by a significantly higher LE activity compared to the controls (p = 0.000000). Cluster analysis made it possible to identify two immunotypes that differed in LE activity. In the 1st cluster, LE activity was within the control range and below, it mainly included patients of the 1st follow-up group (68.3%). In the 2nd cluster LE activity exceeded the control values, this cluster mainly consisted of patients of the 2nd follow-up group (85.0%) (χ2 = 27.82, p = 0.0000).Conclusion: the revealed reliable differences in the distribution of follow-up groups for immunological clusters indicate the possibility of using indicators of LE and α1-PI activity for diagnosing and predicting the dynamics of mild cognitive decline.

Markers of Systemic Inflammation in Assessing the Effectiveness of Neurocognitive Rehabilitation in Aged Patients with Mild Cognitive Impairment

Background: the results of previous studies suggest that the level of activation of inflammatory responses in the periphery correlates with the severity of cognitive impairment in patients with neurodegenerative diseases and can serve as an indicator of the activity of the current pathological process in the brain. Epigenetic factors are suggested to influence the regulation of (neuro)inflammation and cognitive recovery in elderly patients, which opens up a wide spectrum of therapeutic strategies for the treatment of age-associated diseases. Objective: to evaluate the possible effects of a comprehensive neurocognitive rehabilitation program on cognitive functioning and blood immunological parameters of elderly patients with mild cognitive impairment (MCI).Patients and methods: 507 participants of the “Memory Clinic” rehabilitation program with signs of MCI (F06.7, F06.78 according to ICD-10) were examined before the start of neurocognitive training and after its completion (after six weeks). Some patients (11.6%) were observed clinically one year after their inclusion in the program. Cognitive status was assessed using the Modified Hachinski Ischemic Scale, the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the Clock Drawing Test. Enzymatic activity of leukocyte elastase (LE), functional activity of α1-proteinase inhibitor (α1-PI), and levels of antibodies to S-100B and myelin basic protein were determined in patients’ blood. The parameters of healthy donors were used as controls.Results: immunological examination of patients before the rehabilitation program revealed increased LE and α1-PI activity in the overall group compared to controls (p < 0.001 and p < 0.05). Using a previously developed regression model to identify a high-risk group for Alzheimer’s disease (AD) among patients with MCI, all subjects were divided into two groups (cut-off value p = 0.65). Group 1 (low-risk of AD, n = 330) was characterized by increased LE activity and α1-PI (p < 0.001), Group 2 (highrisk of AD, n = 177) was distinguished by decreased LE activity (p < 0.001) accompanied by high α1-PI activity (p < 0.001). After neurocognitive training, differently directed variants of the dynamics of immunological parameters associated with the severity of patients’ cognitive impairment on psychometric scales were identified in each group. For the most of the examined patients (61.3%) the training program turned out to be effective, which was confirmed by the positive dynamics of the psychometric scores and relative normalization of the blood inflammatory markers (p < 0.05). The highest effect of the rehabilitation program was typical for patients not included in the high-risk group for AD (p < 0.001). Follow-up examination revealed stabilization of cognitive functioning in 93.2% of those examined, most of whom were patients with an initially low risk of developing the disease (p < 0.01).Conclusion: neurocognitive rehabilitation of patients with MCI carried out in the “Memory Clinic” conditions can be considered as a social epigenetic factor modulating the current pathological process in patients with cognitive disorders, which is confirmed by objective immunological markers.

Risk of Alzheimer’s disease in patients with the syndrome of mild cognitive impairment, amnestic type (cluster analysis)

IntroductionThe creation of mathematical models for determining the risk of Alzheimer’s disease in patients with mild cognitive impairment based on immune markers of blood is important for differential diagnosis of AD, assessment of the clinical state of patients at different stages of the disease, and optimization of therapy.ObjectivesTo assess the risk of AD in patients with amnestic type of mild cognitive impairment (aMCI) with the use of such markers of inflammation as enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI).MethodsThe object of mathematical analysis on the basis of cluster analysis and logistic regression was the database, including the results of the above immunological parameters (enzyme activity of LE and functional activity of α1-PI.) in plasma of 78 patients with aMCI receiving outpatient treatment in the clinic of FSBSI “Mental Health Research Centre”. Among the examined patients there were 25 men and 53 women aged 44 to 89 years (69.1 ± 9.95).ResultsClustering by k-means and classification by logistic regression indicate the risk of developing AD in patients with aMCI depending on the activity of LE and α1-PI in blood plasma. The total coincidence of objects included in the clusters and in the AD risk group was 94%.ConclusionsThe high coincidence of the two different methods of grouping confirms the previously stated position on the possibility of identifying patients with a high risk of AD among patients with aMCI in the activity of LE and α1-PI in the blood of patients.DisclosureNo significant relationships.

Immunological Indicators of Infl ammation in Late-Life Bipolar Disorder

The aim of the study was to determine the immune markers of infl ammation in the blood plasma of the elderly patients with bipolar affective disorders (BD) in relation to the clinical specifi cities of the disease. Patients and methods: 134 blood samples from the elderly patients aged from 52 to 88 years old (mean age 66.7 ± 7.7 years) with diagnose of bipolar disorder were examined. Infl ammatory markers in the blood plasma were determined as follows: the enzymatic activity of leukocyte elastase (LE) and the functional activity of the D1-proteinase inhibitor (D1-PI), as well as the level of autoantibodies (aAB) to S100b and myelin basic protein (MBP), and the protease inhibitor index (PII), which was the ratio of LE and D1-PI activity and characterized the activity of the proteolytic system as the most important component of infl ammation. Cluster analysis was used to reveal immunotypes. Results and discussion: а signifi cant increase in D1-PI and the level of aAB to S100b was revealed in elderly patients diagnosed with bipolar disorders, as well as low proteolytic activity of infl ammation (according to PII). Immune markers of infl ammation in different types of affective episodes (depressions, manias, mixed affective states) and in therapeutic remission did not differ from each other. Immunological parameters in elderly patients with bipolar disorders depended on the severity degree of the affective disorder. A relationship was found between the severity of depression and the level of aAB to S100b; the difference between mania and hypomania in terms of LE and PII activity was shown; in mixed affective states immunological parameters differed from the control only in moderate disorders. Remission with residual symptoms differed from asymptomatic therapeutic remission in terms of LE and PII activity. The two identifi ed clusters (immunotypes) differed in the activity of LE and PII. Conclusion: the results indicated the participation of infl ammation in the pathogenesis of bipolar disorder, and the isolated immunotypes confi rmed the clinical diversity of the disease. The study of the pathogenetic signifi cance of infl ammation and the identifi cation of various immunotypes was aimed at search for new therapy targets, taking into account the contribution of infl ammation.

Predicting the Risk of Depression in the Elderly by Immunological Indicators Research

Objective: to construct a mathematical model that predicts the state of depression by immunological parameters in the blood plasma of older people to further predict the development of the disease.Patients and methods: 55 hospitalized patients of late age (mean age 69.2 ± 6.9 years) with a depressive episode were included in the study. The control group consisted of 41 elderly people (average age 66.6 ± 6.2 years) without depressive disorders. The activity of inflammatory and autoimmune markers in the blood plasma of patients and control groups was determined: the enzymatic activity of leukocyte elastase (LE), the functional activity of the α1-proteinase inhibitor (α1-PI), the level of autoantibodies to neuro-specific antigens S100B and the myelin basic protein (MBP). Statistical data processing was performed using the R (R version 3.2.4) and STATA (version 12.1) programs. We used point-bead-correlation to measure the strength and direction of the relationship between the binary variable and continuous variables and logistic regression to predict the probability of occurrence of events of interest by the values of one or more independent variables (predictors).Results: in patients with depressive disorders, a statistically significant increase in the functional activity of α1-PI (p ≤ 0.05) and the level of autoantibodies to the neurospecific S100B antigen (p ≤ 0.05) was revealed compared with the control. LE activity and MBP level did not differ from the control (p = 0.12 and p = 0.1, respectively). Based on immunological parameters in elderly patients with depression, a mathematical model is constructed. The accuracy of the correct prediction of outcomes using the model as a whole was 83.33%, which indicates a high predictive efficiency of this model.Conclusion: the results of mathematical analysis obtained in this work indicate that immunological parameters such as the functional activity of α1-PI and S100B are statistically significantly associated with the likelihood of depression in the elderly. Indicators such as enzymatic activity of LE and the level of autoantibodies to MBP did not have a statistically significant effect on the desired probability.

Evidence-Based Psychiatry: Paraclinical Diagnostics of Asthenic Syndrome in Schizophrenia Based on the Determination of Leukocyte-Inhibitory Index

A leukocyte-inhibitory index (LII) is the ratio of the proteolytic enzyme leukocyte elastase (LE) to its inhibitor, an α1- proteinase inhibitor (α1-PI). LII characterizes the activity of the proteolytic system and can be considered as a potential objective criterion that determines both the course and the outcome of the disease. The changes of LII in schizophrenia patients with clinically diagnosed asthenia (schizoasthenia) and patients with schizophrenia without clinical signs of this syndrome were revealed. The objective: to study the possibility of the 95% confidence intervals for a comparative assessment of LII in patients with schizoasthenia and patients with schizophrenia without clinical signs of asthenic syndrome to obtain correct statistical conclusions. Patients and methods: Overall, 95 patients aged 20–55 years with paroxysmal-progressive (F20.x1) and paranoid (F20.00) schizophrenia were examined: 61 patients in the total sample were clinically diagnosed with asthenic symptom-complex. The enzymatic activity of LE and the functional activity of α1-PI were determined in blood serum. LII was calculated according to the formula. The confidence intervals were built using 4 different methods: Fieller’s theorem, delta method, regression methods and bootstrap method. Results: the statistical analysis indicates that the 95% confidence intervals of these indicators for the examined patient groups do not overlap. Therefore, these indicators relate to different populations, which mean the examined groups are characterized by different variants of the ratio of the proteolytic system components. Conclusion: the assessment of LII can serve as an objective statistically correct criterion for presence or absence of asthenic disorder in patients with schizophrenia in addition to clinical examination.

Some inflammation factors and immunophenotypes of depression in elderly patients

To search for the immunological features of depressions in elderly patients, select certain immunophenotypes and analyze their possible connection with clinical and psychopathological features of depression of old age. The study included 55 inpatients of old age (median 68 years) with a depressive episode of mild or moderate severity. The control group consisted of 41 elderly people (median 67 years) without depressive disorders. Clinical, psychometric, immunological and statistical methods were used. The rating scales were HAMD-17 and MMSE. The activity of inflammatory and autoimmune markers, including enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to neurospecific antigens S-100B and myelin basic protein, in the serum of patients and control subjects was determined. The scatter in the immunological parameters both in the direction of exceeding the average values and their decrease was shown in the group of depressed elderly patients compared to the controls. Cluster analysis revealed two immunophenotypes of elderly patients with depression. Immunophenotype A is a group of patients with increased PE activity and immunophenotype B is a group of patients with decreased LE activity (p<0.0000). Immunophenotype A includes patients with complex depressions, comorbid with anxiety and senesto-hypochondriac disorders. In immunophenotype B, patients with prolonged apatic/adynamic depressions (p<0.05), with an earlier onset and longer duration of the disease, with incomplete remissions and more burdened with cardiovascular diseases were more common (p<0.05).

Features of the dynamics of inflammation and apoptosis markers in patients with different acute post-stroke period

The purpose of this was to study the dynamics of markers of inflammation and apoptosis in the serum of patients with ischemic stroke in the early post-stroke period. Materials and methods. The study involved 22 patients (mean age 60 ± 5.5 years) with different dynamics of neurological symptoms in the acute post-stroke period. Patients were examined twice: on the 1st and 10th day of observation. Quantitative assessment of the severity of neurological deficit using ESS and NIHSS scales was carried. Enzymatic activity of leukocyte elastase, functional activity of a1-proteinase inhibitor, level of autoantibodies to MBP (inflammatory markers), as well as the content of p53 and Bcl-2 proteins (markers of apoptosis) were determined in serum. The control group consisted of 35 somatically healthy people of the appropriate age and sex. Results. Identified the different features of the spectrum of the analyzed markers of inflammation and apoptosis in patients with positive and negative dynamics of neurological symptoms in the acute period of ischemic stroke assessed according to the ESS and NIHSS scales. The observed clinical and biological relationships reflect the features of the course of the early post-stroke period and can be considered as possible predictors of the development trajectory of acute brain ischemia.

MARKERS OF INFLAMMATION IN THE BLOOD PLASMA OF PATIENTS WITH FRONTOTEMPORAL DEMENTIA

The aim of this work was to identify several markers of inflammation in the blood of patients with frontotemporal dementia (FTD). 34 patients were surveyed with FTD. The control group consisted of 35 age- and sex- matched healthy people. Blood plasma was used for immunological studies. The enzymatic activity of leukocyte elastase (LE) and the functional activity of the α1-proteinase inhibitor (α1-PI) were determined by a spectrophotometric method, the concentration of interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by ELISE. A statistically significant increase in α1-PI activity (p &lt; 0.0001) was detected in patients with FTD; no difference from control was found for other indicators. There is a significant variation in all indicators, i.e. both increase and decrease of values compared to the control group. According to the level of LE activity, two immunophenotypes were identified. 73.5% of patients with FTD have an immunophenotype characteristic of patients with endogenous psychosis and 26.5% of patients have an immunophenotype similar to Alzheimer’s disease. The data obtained indicate the involvement of inflammatory reactions in the development of FTD and the heterogeneity of this disease as assed by immunological parameters.

Cluster analysis of immunological serum markers in patients with Parkinson’s disease

Introduction. The study of patients’ biological features, including their immune responses, in specific diseases, is an important step towards personalized diagnosis and treatment. Parkinson’s disease (PD) is thus of particular interest as one of the most common age-related neurodegenerative diseases. Study aim – to determine the immunophenotypes of patients with PD using cluster analysis. Materials and methods. Mathematical analysis was conducted on a database of 46 patients with PD. The levels of the following functionally related inflammatory markers were used as the classification characteristics: the enzymatic activity of leukocyte elastase (LE), the functional activity of α1-proteinase inhibitor (α1-PI), the auto-antibody levels to S-100b and myelin basic protein. Results. Based on the immunological markers, the use of multiple algorithms in the cluster analysis of the PD database allowed to obtain two consistent clusters. The patients in cluster 1 were characterized by a high level of LE activity and a low level of functional α1-PI activity, which indicates insufficient serum antiproteolytic capacity and is an unfavourable prognostic indicator for further development of the inflammation-associated pathological process in the brain tissue. The patients in cluster 2 were characterized by increased functional α1-PI activity in the serum, increased S-100b antibody levels and a decreased LE activity as compared with cluster 1, which indicates dysregulation of the inflammatory response, associated with insufficient neutrophil degranulation, whereas elevated autoantibody levels to the neural antigen S100b characterize the most severe lesions in the nervous system. Conclusion. The results of the cluster analysis enable the identification of two immunophenotypes in patients with PD, indicating that a phenotypically similar presentation can be due to a different spectrum of immune markers. The obtained data will serve as a basis for development of an immunological approach to personalized diagnosis and treatment.

Quantitative Evaluation of Links between Inflammatory Markers and Alzheimer’s Disease

Objectives. To obtain quantitative assessment of the link between Alzheimer’s disease (AD) and inflammatory markers such as the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) using a logistical regression model, which was then applied to predicting the probability of AD in patients with mild cognitive impairment syndrome (MCI). Materials and methods. Mathematical analysis was run using a database containing the results of measurements of these immunological parameters (enzymatic activity of LE and functional activity of α1-PI) in the plasma of 91 patients with verified diagnoses of AD on in-patient or out-patient treatment and 37 healthy subjects of comparable age without clinical indications of somatic or mental pathology. Results and conclusions. A logistical regression model was constructed linking LE and α1-PI with the probability that a patient has AD. The model has favorable statistical properties and high predictive effectiveness. These results allow individual patients’ LE and α1-PI values to be used to generate quantitative probabilities that patients have AD.

ESTIMATION OF LEVEL OF SUBPOPULATION CD14&lt;sup&gt;+&lt;/sup&gt;/CD16&lt;sup&gt;+&lt;/sup&gt; MONOCYTES IN PATIENTS WITH JUVENILE DEPRESSIONS

At present, at least two phenotypically different subpopulations of blood monocytes have been identified: "classical" monocytes with the phenotype CD14 ++ /CD16 - and "nonclassical" (pro-inflammatory) with the phenotype CD14 + /CD16 + . It has been established that monocytes CD14 + /CD16 + participate in latent or so-called systemic non-infectious inflammation in the human body along with blood neutrophils and microglial cells of the brain, which are the analogue of monocyte/macrophage system in the brain. Monocyte function disorders are considered as one of the links in the neurodegenerative process underlying the neuroinflammatory hypothesis of the development of schizophrenia. In this connection, the aim of this research was to study in patients with juvenile depression the amount of pro-inflammatory monocytes in terms of the expression level of CD14 + /CD16 + receptors as well as the activity of leukocyte elastase and a 1-proteinase of elastase inhibitor. It was also interesting to determine the mechanisms of their interaction in the pathogenesis of immunosuppression, in particular, to identify a possible connection of pro-inflammatory monocytes with the activity of leukocyte elastase and a 1-proteinase of elastase inhibitor in patients with juvenile depression at the early stage of disease. 27 male patients aged 17-23 years were examined. The disease diagnostics was carried out in accordance with the criteria of ICD-10 according to which all patients have depression with the syndrome of attenuated psychotic symptoms ( Attenuated Psychotic Syndrome) in the structure of psychopathological disorders. 12 mentally healthy age- and gender-matched persons were examined as controls. Monocytes were obtained by the conventional method of adhesion to the plastic surface from mononuclear cells isolated from peripheral venous blood of patients and healthy controls by centrifugation in a ficoll-urographin density gradient (ρ = 1.077). In the blood of patients and healthy controls, the level of monocytes with the phenotype CD14 + /CD16 + , the enzymatic activity of leukocyte elastase and the functional activity of α1-proteinase inhibitor were studied. The clinical and laboratory study showed an increase of more than twofold in the level of the pro-inflammatory subpopulation of CD14 + /CD16 + monocytes in patients compared with its level in healthy individuals. The increase was accompanied by an elevation of leukocyte elastase and a 1-proteinase inhibitor activity. A positive correlation was found between the increase of surface receptors CD14 + /CD16 + expression on monocytes and elevation of the leukocyte elastase activity. These results confirm participation of CD14 + /CD16 + monocytes in the development of latent or non-infectious immune inflammation, and determine the mechanisms of possible interaction between monocytes and neutrophils in the development of immune inflammation in patients with juvenile depressions with the Attenuated Psychotic Syndrome.

Маркеры воспаления в крови пациентов с лобно-височной деменцией

The aim: to identify a number of markers of inflammation in the blood of patients with frontotemporal dementia (FTD). Material and methods : 34 patients with FTD were examined. The diagnosis of FTD was established according to the diag-nostic criteria of the International consortium 2011. The control group consisted of 35 people, comparable in age and sex with patients with FTD. Blood plasma was used for immunological studies. The enzymatic activity of leukocyte elastase (LE) and the functional activity of D1-proteinase inhibitor (D1-PI) were determined by spectrophotometric method, the concentration of interleukin-6 (IL-6), C-reactive protein (CRP) and the level of autoantibodies to S100b and myelin basic protein (MBP) were determined by enzyme immunoassay. Results: patients with FTD showed a significant increase in the activity of D1-PI compared with the control (p < 0,001). Other indicators did not differ from the control ones. However, a significant variation of all studied parameters was revealed,both the excess of values and their decrease relative to the control. For example, the scatter of LE activity was from 127 to 276,5 nmol/min u ml. According to the level of LE activity, two immunophenotypes were identified: 47% of patients with FTD are characterized by a proinflammatory immunophenotype with an increase in inflammatory marker values, and 53% of patients with FTD are characterized by a proinflammatory immunophenotype with insufficient neutrophil activity, similar to Alzheimer's disease. Conclusion: the findings indicate the involvement of inflammatory reactions in the development of FTD and the heterogeneity of this dementia in terms of immunological parameters.

Immunological predictors of acute post-stroke period

At the present time, there is an increased interest in the search for biological predictors of the course and outcome of ischemic stroke (IS). Numerous studies have shown the relationship between neuroinflammation (in the brain) and systemic inflammatory response (in the blood). To study the relationship of inflammatory and autoimmune markers in blood serum of patients with acute ischemic stroke (on the 1st day) with the dynamics of the severity of neurological deficit (on the 1st and 10th day) and to assess the predictive ability of these indicators. Twenty-two patients in the acute period of IS (mean age 60±15.5 years) were examined. The severity of neurological deficit was assessed by ESS and NIHSS. The enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to S-100B and MBP in serum was determined. The control group consisted of 33 healthy subjects. Blood samples were carried out on the 1st day of the post-stroke period, the clinical examination was performed on the 1st and 10th day of observation. Depending on the dynamics of neurological symptoms by the 10th day of observation, two subgroups of patients were identified. The1st subgroup was characterized by the normalization of neurological deficit (n=10). In the 2nd group, the negative dynamics of neurological deficit/lack of any positive changes was observed (n=12). Both subgroups demonstrated the increase in the LE and α1-PI activity as compared to the control (p=0.0019, p=0.00079; p=0.038, p=0.00041, respectively). The highest LE activity was detected in the 1st subgroup (p=0.035). The high level of autoantibodies to MBP was also observed in the 1st subgroup as compared to the control and the 2nd group (p=0.047, p=0.03, respectively). The 2nd subgroup was characterized by a higher functional activity of acute phase protein α1-PI (p=0.04). Using regression analysis, a model for predicting the course of the early post-stroke period depending on the determined immunological parameters was developed. The results suggest that the studied inflammatory and autoimmune markers may be possible predictors of the course of the early post-stroke period.

Neurobiological parameters in quantitative prediction of treatment outcome in schizophrenic patients.

The aim of the study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic patients. Correlation and regression analyses of quantitative clinical scores (by Positive And Negative Syndromes Scale- PANSS), together with background EEG spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed in 50 patients (all females, aged 32.9±10.8 years) with hallucinatory-delusional disorders in the frames of attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of syndrome based treatment course (at visit1) were matched with PANSS clinical scores of the same patients after treatment course at the stage of remission establishment (at visit2). The multiple linear regression equations were created which contained only 3 to 4 (from initial 80) background EEG parameters and one of four immunological parameters. These mathematical models allowed prediction from 65% to 76% of PANSS scores variance after treatment course (at visit2). The data obtained may be used for elaboration of methods of individual quantitative prediction of treatment outcome in schizophrenic patients.

P.1.014 - Investigating the effect of central nervous system drugs on leukocyte elastase activity in vitro

Participation of immune reactions in the pathogenesis of mental diseases is widely studied. A variety of molecules are involved in the development of inflammatory reactions, one of the analyzed biochemical markers of inflammation is the activity of leukocyte elastase (LE), an enzyme secreted by neutrophils. Due to proteolytic activity towards elastin and collagen, LE is able to disrupt the integrity of the vessels and increase permeability of the blood-brain barrier in case of various brain diseases [1]. The effect of drugs used to treat mental illness (or lack thereof) on the inflammatory component of the pathogenesis of mental diseases seems to be poorly understood. Aim This study was а comparative assessment of the effect of psychotropic (chlorpromazine, imipramine) and nootropic (cerebrolysin, ceretone) drugs on LE activity in an in vitro experiment. Material and Methods LE activity was measured in a pool of blood plasma of healthy people with solutions of drugs: chlorpromazine; imipramine; choline alphoscerate; cerebrolysin in different concentrations, including therapeutic ones. Enzymatic activity of LE was determined by spectrophotometric method. Statistical comparison of multiple groups was carried out using ANOVA and Newman-Keuls test, values of p Results А dose-dependent inhibitory effect of chlorpromazine was revealed. In the range of concentrations from 1.25 μg/ml to 40 μg/ml, including therapeutic one of 5-10 μg/ml, LE activity was significantly lower compared to control (p Different concentrations (0.00375 mg/ml - 3.75 mg/ml) of choline alfoscerate had no influence on LE activity (p = 0.33). Cerebrolysin at concentrations from 0.043 mg/ml to 2.15 mg/ml also had no influence on LE activity, however, at concentration 4.3 mg/ml, which corresponds to a double maximum dose, cerebrolysin had a potentiating effect on LE, whose activity significantly increased by 17.5% compared to control (p Conclusion Thus, it has been shown that psychotropic drugs such as chlorpromazine and imipramine have an inhibitory effect on LE activity in an in vitro experiment, while nootropic cerebrolysin can activate LE. The obtained data indicate that these drugs, used in the treatment of mental illness, can influence inflammatory response, which is important in the pathogenesis of mental disorders.

Quantification of the relationship between inflammatory markers and Alzheimer's disease

To quantify the relationship of Alzheimer's disease with the inflammatory markers: enzymatic activity of leukocyte elastase (LE) and functional activity of α1-proteinase inhibitor (α1-PI) on the basis of the logistic regression model and to build a model to predict the probability of AD in patients with mild cognitive impairment (MCI). The object of the mathematical analysis was the database, which included the results of assays of LE activity and functional α1-PI activity in blood plasma of 91 patients with a verified diagnosis of AD in inpatient or outpatient treatment and 37 age-matched healthy people. The logistic regression model connecting LE and α1-PI with the probability of AD is built. The model has good statistical properties and high predictive efficiency. The results allow to obtain the quantitative estimate of the probability of AD by individual values of LE and α1-PI in patients with MCI.