RESUMEN
OBJECTIVE: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters. MATERIAL AND METHODS: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant (p<0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period. CONCLUSION: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.
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Disfunción Cognitiva , Demencia , Glicerilfosforilcolina , Humanos , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/tratamiento farmacológico , Femenino , Masculino , Anciano , Demencia/prevención & control , Estudios Prospectivos , Glicerilfosforilcolina/uso terapéutico , Glicerilfosforilcolina/administración & dosificación , Resultado del Tratamiento , Persona de Mediana Edad , Progresión de la Enfermedad , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: To assess clinical and psychopathological characteristics of late-aged female patients with late-onset psychoses in clusters formed on the basis of biochemical and immunological blood parameters. MATERIAL AND METHODS: We examined 59 women with schizophrenia and schizophrenia-like psychoses with onset after 40 years (ICD-10 F20, F22.8, F25, F23, F06.2), including 34 women with late-onset (40-60 years) and 25 with very late onset psychoses (after 60 years). At the time of hospitalization, a clinical/ psychopathological study was carried out using CGI-S, PANSS, CDSS, and HAMD-17, as well as the activities of glutathione reductase (GR) and glutathione-S-transferase (GT) have been determined in erythrocyte hemolysates, and the activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) have been assessed in blood plasma. Biochemical and immunological parameters have been also determined in 34 age-matched mentally healthy women. RESULTS: Clustering by signs such as GR, GT, LE and α1-PI has yielded two clusters of objects (patients) significantly different in GT (p<0.0001), LE (p<0.0001), and α1-PI (p<0.001) activities. Relatively to the controls, in the cluster 1 patients, the activities of GST and α1-PI are increased, the activity of LE is decreased, whereas, in the cluster 2 patients, the activity of GR is decreased, and the activities of LE and α1-PI are increased. Cluster 1 patients differ from cluster 2 patients in greater severity of the condition (CGI-S, p=0.04) and higher total scores on PANSS subscales' items. Cluster 1 includes 76% of patients with very late onset. Different correlations between clinical and biological signs are found in two clusters. CONCLUSION: The identified clusters have different clinical and psychopathological characteristics. Dividing patients into subgroups according to biochemical and immunological parameters is promising for the search for differentiated therapeutic approaches.
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Edad de Inicio , Trastornos Psicóticos , Esquizofrenia , Humanos , Femenino , Esquizofrenia/sangre , Persona de Mediana Edad , Adulto , Trastornos Psicóticos/sangre , Trastornos Psicóticos/diagnóstico , Glutatión Transferasa/sangre , Glutatión Reductasa/sangre , Elastasa de Leucocito/sangre , Anciano , Psicología del EsquizofrénicoRESUMEN
OBJECTIVE: To determine the indicators of systemic inflammation in peripheral blood samples of patients with organic non-psychotic disorders. MATERIAL AND METHODS: The study included 60 patients, aged 56.9±7.7 years, with a disease duration of 7.3±5.55 years, with a verified ICD-10 diagnosis «Organic emotionally labile (asthenic) disorder¼ (F06.6) and «Organic Anxiety Disorder¼ (F06.4). Patients with organic asthenic disorder were divided into two groups according to the prevailing symptoms: 36 patients with asthenic-cephalgic syndrome (AC); 10 patients with astheno-dysthymic syndrome (AD); the third group (n=14) included patients with organic anxiety disorder (AND). The control group consisted of 65 people matched for age and sex with patients. The activity of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined by the spectrophotometric method, the levels of aAB to S100b and MBP were determined by ELISA. The protease-inhibitory index (PII), i.e., the ratio of LE activity to α1-PI, was calculated. RESULTS: A significant increase in LE (235.4 [216.4; 258.1] nmol/min*ml, p<0.001), the functional activity of α1-PI (43.1 [38.7; 47.6] u/ml, p<0.001), the level of aAB to S100b (0.78 [0.70; 0.89] opt.units, p<0.05) and a decrease in PII (6.19 [5.32; 6.9], p<0.05) in the group of patients with organic non-mental disorders compared with controls were shown. Deviations from the normal values of immune markers of inflammation in blood samples were also found in various syndromes. Clustering of the total group of patients by LE activity made it possible to identify 2 immunotypes with a balanced and unbalanced inflammatory process, confirming the clinical diversity of the disease: 60% of patients with AC syndrome belong to the 1st cluster, in which the ratio of immune markers characterizes a balanced inflammatory process aimed at restoration of homeostasis; 80% of patients with organic AND belong to the second cluster, which characterizes low proteolytic activity and imbalance of inflammation, which is an unfavorable prognostic factor in terms of the further course of the disease and therapy. CONCLUSION: The results confirm the importance of the inflammatory link in the neuroprogression of organic non-psychotic disorders. The identified features of the immune response can serve as an additional paraclinical criterion for differential diagnosis and evaluation of the prognosis of the further development of the disease.
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Astenia , Trastornos Psicóticos , Humanos , Biomarcadores , Inflamación/diagnóstico , Trastornos de la Personalidad , Elastasa de Leucocito , alfa 1-AntitripsinaRESUMEN
OBJECTIVE: To evaluate the change of a number of clinical and immunological parameters of patients with amnestic type Mild Cognitive Impairment (aMCI) in the course of therapy with Choline alfoscerate (α-GPC) in order to develop a monitoring and predicting system of its effectiveness in people at risk for Alzheimer's disease. MATERIAL AND METHODS: Thirty patients with aMCI, aged 56 to 82 years (mean age 68.8±9.4 years), received course therapy with α-GPC in capsules of 400 mg 3 times a day (1200 mg per day) for 3 months. Therapeutic efficacy evaluation according to psychometric tests and scales was carried out three times (0, 45 and 90 days), immunological parameters of leukocyte elastase (LE) and α1-protease inhibitor (α1-PI) were evaluated twice on days 0 and 90 of therapy. RESULTS: A good therapeutic effect over the course treatment with α-GPC, both in terms of cognitive functioning and a number of immunological parameters in patients with aMCI was shown. Significant clinical and immunological correlations included both an improvement in cognitive functions (according to MMSE and the Boston Naming Test) and an increase in LE activity level after the completion of a course of α-GPC therapy, which suggest that an increase in LE functional activity can be considered as a potential marker of a positive therapeutic response to α-GPC treatment in aMCI patients. CONCLUSION: This study shows high significance of further research in assessing the role of immune mechanisms of α-GPC therapeutic efficacy in aMCI patients and the possibility of using immunological parameters as prognostic markers of its therapeutic effect.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Persona de Mediana Edad , Anciano , Glicerilfosforilcolina/uso terapéutico , Pruebas Neuropsicológicas , Disfunción Cognitiva/psicología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , CogniciónRESUMEN
OBJECTIVE: The comparison of inflammatory markers in different age groups of patients with endogenous depression and correlation of immunological parameters with the clinical features of depression. MATERIAL AND METHODS: The study included 140 patients with endogenous depression (ED) (F21, F31-F34, ICD-10) aged 15 to 82 years (39.8±23 years), including 55 patients of adolescent age (18.9±2.8 years), 30 middle-aged patients (38.7±10.3 years) and 55 elderly patients (69.1±7.1 years). The total duration of the disease differed from 5 months to 45 years. Psychometric assessment of patients was carried out using HDRS. The control groups consisted of 143 healthy people aged 16 to 75 years. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), their ratio (leukocyte-inhibitory index, LII), the levels of antibodies to S100B and myelin basic protein (MBP) were determined in blood. RESULTS: Three immunological clusters were identified that correspond to different clinical variants of ED. A pro-inflammatory status with an activation of the leukocyte-inhibitory system is characteristic of 52.9% of patients (cluster 1). The clinical feature of this status is predominantly «classic¼ ED in the form of anxious, anxious-melancholic or anxious-apathetic depression without pronounced negative symptoms. Two other clusters are characterized by the imbalance of leukocyte-inhibitory system associated with insufficient a1-PI activity (cluster 2) and with insufficient LE activity (cluster 3). A common clinical feature of such ED is an atypical course with the predominance of apathetic-adynamic and dysphoric depression, the presence of negative disorders and a poor prognosis. The imbalance of leukocyte-inhibitory system associated with insufficient LE activity is typical mainly for elderly patients and is characterized by a longer duration of disease. CONCLUSIONS: The status of leukocyte-inhibitory system of inflammation is correlated with the clinical features of ED in different age groups of patients. LII can be considered as an additional paraclinical criterion for differential diagnosis and prognosis of ED.
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Trastorno Depresivo , Elastasa de Leucocito , Adolescente , Adulto , Anciano , Autoanticuerpos , Humanos , Inflamación , Leucocitos , Persona de Mediana Edad , Adulto Joven , alfa 1-AntitripsinaRESUMEN
OBJECTIVE: To identify levels of inflammation markers (the enzymatic activity of leukocyte elastase (LE), the functional activity of the α1-proteinase inhibitor (α1-PI), autoantibodies to neurotrophin S100b and myelin basic protein (MBP)) in blood plasma of old- and young-aged patients with schizophrenia in comparison with features of the clinical course of schizophrenia. MATERIAL AND METHODS: Two age groups of patients with schizophrenia were examined. The 1st group consisted of 19 female patients, aged 60 to 78 years (mean age 67.3±5.4 years), with disease duration from 0.5 months to 29 years (9.7±7.6). The 2nd group comprised 24 female patients, aged 19 to 42 years (mean age 26.8±6.3 years), with disease duration from 0.15 to 6.6 years (3.3±2.4). Nineteen age-matched healthy women were included in two control groups. Inflammatory and autoimmune markers were measured in blood plasma using «Neuro-immuno-test technology¼. RESULTS: In the 1st group, a relative smoothness and rigidity of the productive symptoms profile, a reduction of disease progression and a tendency to the development of negative symptoms were established. The 2nd group was characterized by polymorphism, severity and dynamism of productive disorders, as well as the progression and lability of the schizophrenic process. The most significant differences in the spectrum of the analysed immune markers relate to the ratio of the activity of LE and its inhibitor α1-PI, i.e. proteinase-inhibitory index (PII). CONCLUSIONS: The identified multidirectional changes of PII in elderly patients compared to the controls may reflect the imbalance of the inflammatory response and the role of this imbalance in shaping the characteristics of psychopathological symptoms in these patients.
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Esquizofrenia , Adulto , Anciano , Biomarcadores , Femenino , Humanos , Inflamación , Elastasa de Leucocito , Persona de Mediana Edad , Esquizofrenia/diagnóstico , Adulto Joven , alfa 1-AntitripsinaRESUMEN
OBJECTIVE: To determine factors of innate and acquired immunity in adaptation disorders with a predominance of asthenic or anxiety-depressive syndrome. MATERIAL AND METHODS: Twenty-five patients with ICD-10 diagnosis of «Adaptation Disorders¼ (F43.2), including 9 with asthenic syndrome and 16 with anxiety-depressive syndrome, were examined. The control group consisted of 23 healthy individuals. The relative number of lymphocyte phenotypes was determined by flow cytometry; the concentration of IgM, IgG, IgA, aAB to S100b and MBP - by ELISA; CIC level - by the method of selective precipitation with PEG-6000; phagocytic activity of neutrophils by a test system with melamine-formaldehyde latex; activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) by a spectrophotometric method. RESULTS: There were significant changes in the parameters of acquired immunity in the group with asthenic syndrome and those of innate immunity in the group with anxiety-depressive syndrome. An increase in α1-PI activity, in the total number of significant correlations between different immunological parameters, in the involvement of α1-PI in integration of acquired and innate immunity were observed in the anxiety-depressive group compared with the asthenic group. CONCLUSIONS: The peculiarities of stress response in patients with leading anxiety-depressive syndrome are the high activity of α1-PI, which, along with the strengthening of correlation intersystem associations and the involvement of this protein in the integration of acquired and innate immunity, allows us to consider α1-PI as a criterion that improves the accuracy of diagnosis of the nature of the course of adaptation disorders.
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Inmunidad Adaptativa , Elastasa de Leucocito , Astenia , Humanos , Inmunidad Innata , alfa 1-AntitripsinaRESUMEN
AIM: 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. MATERIAL AND METHODS: 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. RESULTS AND CONCLUSION: 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).
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Inflamación , Elastasa de Leucocito , Anciano , Autoanticuerpos , Biomarcadores , Humanos , alfa 1-AntitripsinaRESUMEN
AIM: To determine immunophenotypes of patients with adaptation disorders using cluster analysis. The level of inflammatory markers such as leukocyte elastase (LE) enzyme activity and functional activity of α1-protease inhibitor (α1-PI) were used as a classifying attribute (characteristic). MATERIAL AND METHODS: The results of evaluation of enzymatic activity of LE and functional activity of α1-PI in 40 patients with adaptation disorders (ICD-10 F43.2) were subjected to cluster analysis. The control group included 23 age- and sex-matched healthy controls. RESULTS: Several algorithms of cluster analysis allow to identify three immunophenotypes in the group of patients with adaptation disorders. Immunophenotypes differed significantly by ratios of LE and α1-PI activity, which were mostly driven by different LE activity. Cluster 1 with the relatively low LE activity and high background α1-PI, is of particular interest because it may reflect the disturbed interaction between the various links of immune response. CONCLUSION: The obtained results of cluster analysis confirm the hypothesis about the existence of three immunophenotypes in the patients with adaptation disorders, which indicates that a phenotypically similar pattern can be determined by different spectra of immune indices.
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Inflamación , Biomarcadores , Humanos , Elastasa de Leucocito , alfa 1-AntitripsinaRESUMEN
AIM: 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). MATERIAL AND METHODS: 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. RESULTS AND CONCLUSION: 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.
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Enfermedad de Alzheimer , Biomarcadores , Disfunción Cognitiva , Humanos , alfa 1-AntitripsinaRESUMEN
AIM: To identify inflammatory and autoimmune markers (enzymatic activity of leukocyte elastase (LE), functional α1-proteinase inhibitor (α1-PI), the level of autoantibodies to neurospecific antigens S100b and myelin basic protein (MBP)) as well as phagocytic activity of blood neutrophils of patients with disorders of adaptation, to determine certain immunophenotypes and analyze their possible relationships with disease characteristics. MATERIAL AND METHODS: The study included 40 patients with adaptation disorders, mostly women. Diagnostic evaluation and clinical qualification of patients was carried out in accordance with ICD-10: 'Adjustment disorder' (F43.2). The control group consisted of 23 individuals matched for age and sex with patients. The activity of LE and α1-PI was determined by spectrophotometry, and the levels of autoantibodies to S100b and MBP by ELISA, phagocytic activity by the absorptive capacity of neutrophils of peripheral blood of melamine-formaldehyde latex particles. RESULTS: In the total group of patients with adaptation disorders, increased enzymatic activity of LE and functional α1-PI was shown compared to controls (p<0.001 and p<0.0001, respectively). There were no differences in the level of autoantibodies to neuroantigens, and changes in phagocytic index (PhN) compared with the control, however the tendency to reduction of phagocytic number (PhN) was observed. Patients were stratified by leading psychopathological symptoms (predominance of asthenic-depressive or anxious-depressive symptoms, polymorphic symptomatology) and by immunophenotype: (A) inflammatory markers - in the range of control values, (B) - the increase compared to the control activity of both LE and α1-PI, (C) preferential increase in the activity of α1-PI only. The frequency of these immunophenotypes was similar within each of the clinical subgroups. CONCLUSION: The results suggest the involvement of inflammation in the pathogenesis of adjustment disorders due to stress factors. Various immunological variants differed by proportion of inflammatory markers were not associated with clinical symptoms.
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Trastornos de Adaptación , Autoanticuerpos , Biomarcadores , Femenino , Humanos , Elastasa de Leucocito , Masculino , alfa 1-AntitripsinaRESUMEN
AIM: The evaluation of the risk of Alzheimer disease (AD) in patients with cognitive impairment, amnestic type (aMCI) on the basis of cluster analysis and logistic regression 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). MATERIAL AND METHODS: The study object of statistical analysis was the database, including the results of LE activity and functional α1-PI activity in blood plasma of 78 outpatients with aMCI (25 men and 53 women, aged 44 to 89 years (69.1±9.95). RESULTS AND CONCLUSION: Clustering by k-means and classification by logistic regression indicate a high probability of 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%. The high coincidence of two different methods of grouping confirms the previously stated notion of the possibility of identifying patients with the high risk of AD among patients with aMCI by the activity of LE and α1-PI in the blood.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Adulto , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
AIM: To determine a complex of immune markers reflecting various links of multicomponent inflammatory reactions in amnestic type of mild cognitive impairment (aMCI) in comparison with Alzheimer's disease (AD). MATERIAL AND METHODS: Sixty-seven patients with aMCI, aged 72 [63; 77] years, and 91 patients with Alzheimer's disease at the age of 74 [68; 79] years were examined. The aMCI was diagnosed according to the criteria of R.S. Petersen et al. (1999) and B. Dubois et al. (2014). The diagnosis of AD was established in accordance with the ICD-10 and NINCDS-ADRDA criteria. The degree of dementia severity was determined by clinical signs using the CDR (Clinical Dementia Rating) and the Mini Mental State Examination (MMSE) total score. The control group included 38 age- and sex-matched individuals. Immune and biochemical parameters were determined in blood plasma. The activity of LE and α1-PI was determined by spectrophotometric method. Concentrations of IL-6 and CRP were measured by enzyme immunoassay. RESULTS: AD was characterized by the significant decrease in LE activity (p<0.0001) and increase in the activity/levels of α1-PI, CRP and IL-6 (p<0.001; p<0.05; p<0.01, respectively) compared to controls. CDR and MMSE scores were correlated with the LE activity (r=-0.38, r=0.31, p<0.05), i.e. cognitive decline was associated with decreased activity of LE. aMCI was characterized by the significant increase in the activity/level of α1-PI and IL-6 (p<0.0001; p<0.01). In 30% of patients with aMCI, a spectrum of inflammatory markers, typical for patients with AD, was determined. CONCLUSION: Based on the results of comparative analysis of aMCI and AD, one can suggest that one third of patients with aMCI represents a group of ultra-high risk of AD. These patients need a dynamic follow-up with a regular assessment of the state of cognitive functions and possibly preventive therapy.
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Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/inmunología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/inmunología , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Interleucina-6/sangre , Elastasa de Leucocito/sangre , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , alfa 1-Antitripsina/sangreRESUMEN
AIM: To analyze the correlation between clinical and immunological parameters in children with mental retardation (MR) in order to explore the possibilities of using immunological data in assessing the severity of patient's condition and predicting a risk of decompensation, exacerbation of mental disorders comorbid to MR. MATERIAL AND METHODS: Seventy-three school children, aged 8-17 years, mean age 12,6±2,4 years, with MR of different genesis and 64 physically and mentally healthy children (control group) of the same age and sex were studied clinically and immunologically. The degree of clinical severity of MR was evaluated by CGI-S scale (the Clinical global impression-severity), the level of intellectual disabilities was evaluated by the Wechsler Intelligence Scale. Enzymatic activity of leukocyte elastase; functional activity of α1-proteinase inhibitor; levels of autoantibodies to neurospecific antigens - S-100b and myelin basic protein were analyzed in the serum of patients and healthy children. RESULTS AND CONCLUSION: The activation of the immune system was associated with comorbid to MR current psychopathological disturbances that were more severe, persistent and required long-term maintenance treatment. Analysis of immunological parameters can be used in children with MR treated in outpatient network as an additional test for the detection of mental state decompensation.
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Discapacidad Intelectual/inmunología , Discapacidad Intelectual/psicología , Adolescente , Autoanticuerpos/sangre , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Sistema Inmunológico , Discapacidad Intelectual/sangre , Elastasa de Leucocito/metabolismo , Masculino , Proteína Básica de Mielina/inmunología , Riesgo , Índice de Severidad de la Enfermedad , Adulto Joven , alfa 1-Antitripsina/metabolismoRESUMEN
Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1ß in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1ß by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1ß production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1ß by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.
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Interleucina-1beta/metabolismo , Monocitos/metabolismo , Monocitos/ultraestructura , Esquizofrenia/patología , Adulto , Análisis de Varianza , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Microscopía Electrónica de Transmisión , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
OBJECTIVE: To compare clinical and immunological parameters in children with schizophrenia and to analyze the possibility of using them in the assessment of the pathological process activity. MATERIAL AND METHODS: We examined 62 patients, 39 boys and 23 girls, aged from 4 to 17 years, with childhood-onset schizophrenia. Mental state of the patients was assessed using a psychopathological method and with PANSS and CGI scales. The activity of leukocyte elastase (LE) and alpha(1)-proteinase inhibitor (α1-PI) was measured by spectrophotometric method. ELISA was used to determine the level of autoantibodies to neuroantigenes to S-100B and basic myelin protein. RESULTS AND CONCLUSION: The activation of innate immunity assessed by the activity of LE and α1-PI and adaptive immunity (levels of autoantibodies to neuroantigenes to S-100B and basic myelin protein) was identified. Significant correlations of the level of immune system activation with the severity of patient's state on СGI-S (r=0.64, p=0.000001) as well as scores on the PANSS negative symptom subscale (r=0.34, p=0.0077) were found. The results suggest the possibility of using these immunological parameters for the objectification of clinical state of children with schizophrenia.
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Autoanticuerpos/sangre , Proteína Básica de Mielina/inmunología , Subunidad beta de la Proteína de Unión al Calcio S100/inmunología , Esquizofrenia Infantil/diagnóstico , Esquizofrenia Infantil/inmunología , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Femenino , Humanos , Masculino , Esquizofrenia Infantil/sangre , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To investigate the effect of the neuroleptic aminazine (chlorpromazine) and the antidepressant melipramine on the activity of leukocyte elastase (LE). METHODS: The LE activity was measured on a spectrophotometer. Different doses of aminazine and melipramine in terms of therapeutic doses were added to the pooled blood serum sampled from 7 healthy people. RESULTS: Aminazine and melipramine inhibited the LE activity. CONCLUSIONS: The dose-dependent inhibiting effect of aminazine and melipramine was shown.
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Antidepresivos Tricíclicos/farmacología , Antipsicóticos/farmacología , Clorpromazina/farmacología , Inhibidores Enzimáticos/farmacología , Imipramina/farmacología , Elastasa de Leucocito/antagonistas & inhibidores , Psicotrópicos/farmacología , Humanos , Elastasa de Leucocito/sangreRESUMEN
To analyze the possibility of using immunological parameters for the assessment of the activity of the process and prediction of the quality and completion of remission, we compared the dynamics of clinical and immunological parameters in 76 patients with endogenous attack-like psychoses during pharmacotherapy of a psychotic episode. Authors confirmed evidence for the activation of innate and adaptive immunity in the acute stage of psychosis as well as the correlation between immunological parameters (leukocyte elastase (LE) activity, alpha(1)-proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth factor (Aab-NGF)) and clinical symptoms assessed with the PANSS. The improvement of the clinical state assessed by the reduction in PANSS total score was noted in all patients though there were variations in the dynamics of immunological parameters. The increase of immunological parameters, along with the absence of changes at the discharge from the hospital, suggests that the remission was of low quality and the pathological process did not attenuate. Outpatient examination revealed the different dynamics of psychopathological disorders: stable state in 50% patients, moderate worsening of psychological state in 50% patients. Worsening of clinical symptoms after the discharge and in the outpatient stage was correlated with the elevation of the activity/level of immunological parameters. The changes in LE activity and Aab-NGF level precede the changes in mental state of patients in the following 1-2 months. These parameters may be used for monitoring of patients and prediction of quality and completion of remission.
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Monitorización Inmunológica , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/inmunología , Inmunidad Adaptativa , Adulto , Anciano , Femenino , Humanos , Elastasa de Leucocito/inmunología , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/inmunología , Pronóstico , Adulto Joven , alfa 1-Antitripsina/inmunologíaRESUMEN
OBJECTIVE: To identify inflammatory markers in schizophrenia in aged. MATERIAL AND METHODS: The main group included 29 patients with schizophrenia, mean age 72.1 ± 6.9 years. A comparison group comprised 34 patients with Alzheimer's disease, mean age 73.4 ± 7.9 years. Seven plasma inflammatory indicators were determined. RESULTS: There was a significant increase in the activity/content of acute inflammation stage proteins: α1-proteinase inhibitor and C-reactive protein as well as anti-inflammatory interleukin-10 compared to the controls while the activity of other inflammatory molecules (leukocyte elastase, tumor necrosis factor alpha, interleukin-1 receptor antagonist) was not changed. No correlations between immunological parameters and clinical presentations were found. CONCLUSION: The results suggest that inflammation does not play a significant role in the remote stages of schizophrenia, in contrast to earlier stages of the disease, and the activity of the pathological process decreased in the late stages. These characteristics can reflect the body reactivity in elderly patients.
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Enfermedad de Alzheimer/sangre , Inflamación/sangre , Esquizofrenia/sangre , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Proteína Antagonista del Receptor de Interleucina 1/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Elastasa de Leucocito/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangre , alfa 1-Antitripsina/sangreRESUMEN
The following markers of inflammation: enzymatic activity of leukocyte elastase (LE), functional activity of alpha-1-proteinase inhibitor (α1-PI), levels of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in the blood plasma of patients with Alzheimer's disease (AD) and vascular dementia (VD). The results confirm the presence of an inflammatory component in the pathogenesis of AD and VD. The high level of CRP may be considered as a marker of VD in the early stages of disease. There was an elevation of α1-PI activity in AD patients compared to age-matched controls. The α1-PI activity, levels of CRP and IL-6 increased with the severity of dementia while the LE activity significantly decreased compared to controls (p<0.01). In patients with AD, the IL-6 level was negatively correlated with MMSE scores (Spearman r = -0.46, p=0.0077) and, therefore, can be considered as a biological marker of the severity of the pathological process. Positive correlations between CRP and IL-6 may plausibly reflect an ability of IL-6 to induce the synthesis of CRP.