Cytokines and neurotrophic factors in the severity assessment of children autism.

Due to the steady increase in the number of children with autism and the high heterogeneity of clinical groups, the diagnosis of these disorders and their severity is an urgent problem in modern medicine. In the course of the work, 126 children from 3 to 13 years old with typical neurodevelopment and with severe and mild autism spectrum disorders (ASD) were examined. Disease severity was determined according to the Childhood Autism Rating Scale (CARS). The levels of pro-/anti-inflammatory cytokines and neurotrophic factors (nerve growth factor beta and brain-derived neurotrophic factor) in blood plasma were assessed by enzyme immunoassay. Associations between indicators in each group of patients were assessed using the Spearman test and visualized as a heatmap of correlations. Statistical data processing was carried out in the R software. Significantly high levels of IL-4 in blood plasma and a decrease in the number of significant correlations within/between systems were revealed in children with mild autism compared with children with typical neurodevelopment. Such data can probably reflect the theory that some children with ASD are characterized by slow brain development, as a variant of the evolutionary norm. On the contrary, in children with severe ASD, high systemic levels of IL-6 and IFNg are shown against the background of low values of IL-10, IL-1ß, TNFα and NGFß, supported by the almost complete absence of intra/ and intersystem interactions. This may act as an indicator of maladaptation of the immune and nervous systems in severe autism, which contributes to the pathogenesis of the disease. Thus, a set of indicators: high levels of key pro-inflammatory cytokines - IL-6 and IFNg, low levels of IL-10, NGFß and disintegration of the cytokine and nervous systems in the periphery can be proposed as an approach to indicate the severity of the condition in children with ASD.

Lateral stress profile and fluorescent lipid probes. FRET pair of probes that introduces minimal distortions into lipid packing.

The modern theory of lipid membrane structure incorporates the concept of lateral stress profile. The latter represents the forces that act on any solute inside the membrane. We used this concept to propose two lipid probes that introduce minimal distortions into the lipid bilayer packing: the surface pressure isotherms and volt-potentials of the pure and mixed (probe-containing) lipid monolayers are equal. The probes represent a FRET pair. They are applicable in lipid transfer and vesicle fusion experiments.

Heterodimeric V. nikolskii phospholipases A2 induce aggregation of the lipid bilayer.

We report that the action of the heterodimeric phospholipases A2 (PLA2s) from Vipera nikolskii, which comprises enzymatically active basic subunit and inactive acidic PLA2 homologue, on the lipid bilayer results in the aggregation and stacking of bilayers. These processes are demonstrated using two independent methods (fluorescence spectroscopy and electron microscopy). Aggregation of bilayers is possible because both subunits of the V. nikolskii heterodimer contain a membrane-binding site (also known as IBS). Thus, when the two IBSs bind to the membrane, the heterodimer acts as a connecting agent. Heterodimers induce aggregation of negatively charged bilayers composed of phosphatidylglycerol and do not induce aggregation of neutral bilayers composed of phosphatidylcholine.

[FREE CONSUMPTION OF GLUCOSE SOLUTION BY RATS AS A CRITERION FOR EVALUATION ITS ABSORPTION IN THE SMALL INTESTINE (Experimental study and mathematical modeling)].

The aim of the work is to analyze the relationship between consumption of glucose solution by rats and its absorption, and to use this fact for assessment of the absorptive capacity of the small intestine in non anesthetized animals in vivo. Consumption of glucose solution (200 g/l) by fasted rats was recorded in the control, and after administration of phloridzin--inhibitor of glucose active transport- or 3 hours after the restriction stress. On the mathematical model we studied the relative role of factors that can influence the temporal dynamics of glucose consumption by rats. The rate of glucose consumption was observed being decreased in the presence of phloridzin (1 mM), and be increased after the stress. The results of modeling are consistent with the experimental data and show that the rate of consumption of glucose solutions considerably more depends on the transport activity of the small intestine than on glucose concentration in the solution, or on the substrate regulation of the stomach emptying. Analysis of dynamics of consumption of glucose solution by intact rats may be considered as one of promising approaches to assessing the absorptive capacity of the small intestine under natural conditions.

Secretory phospholipase A2 activity in blood serum: the challenge to sense.

Excess levels of secretory phospholipase A2 (sPLA2) is known to contribute to several inflammatory diseases including vascular inflammation correlating with coronary events in coronary artery disease. Thus a method to monitor sPLA2 activity in blood serum is urgently needed. Such method is still a challenge since existing fluorescent probes do not allow to monitor sPLA2 activity directly in blood serum. Here we analyze and overcome barriers in sPLA2 sensing methodology and report a fluorescent probe and a kinetic model of its hydrolysis by sPLA2. New probe is designed with a fluorophore and a quencher not interfering binding to the enzyme. At the same time phospholipid matrix bearing the probe promotes efficient initial quenching of the fluorophore. Kinetic model of probe hydrolysis takes into account signal change due to the side processes. The probe and the kinetic model applied together prove the concept that the activity of sPLA can be measured directly in blood serum.

[Synthesis of a fluorescent analog of methotrexate lipophilic prodrug].

A fluorescent analog of the lipophilic prodrug of antitumor agent methotrexate has been synthesized. The conjugate consists of a residue of rac-1-[13-(Me4-BODIPY-8)tridecanoyl]-2-oleoylglycerol connected to methotrexate by ester bond via ß-Ala-N-carbonylmethylene linker (Me4-BODIPY-8,4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacen-8-yl). The probe is designed for incorporation in the membrane of liposomal vehicle to study a mechanism of interaction with tumor cells and an intracellular traffic.

[Somatopsychic manifestations in patients with chronic viral hepatitis].

The aim of the work was to study somatopsychic manifestations in patients with chronic viral hepatitis (CVH). MMPI profiles, state and trait anxiety were assessed in 110 patients. Boundary psychic problems were evaluated using the Beck scale. It was shown that mean MMPI T-score in patients with CVH was above 50; half of them developed "neurotic triad"; hypochondria occurred in 37.3%, depression in 42.7%, and hysteria in 37.1%. The highest level of state anxiety was documented in patients with HCV infection and isolated HBCor At. The CVH-1b genotype was associated with enhanced occurrence of depression in patients having virus-positive blood for 1-5 years. The level of state and trait anxiety in them was lower than in patients with duration of viremia over 5 years.

[Quality of life indices in patients with chronic viral hepatitis].

AIM: to estimate quality of life (QL) indices in patients with chronic viral hepatitis (CVH) and their relationships to the clinical characteristics of the disease. SUBJECTS AND METHODS: One hundred and ten patients with chronic viral hepatitis (CVH), including 58 patients with chronic hepatitis C (CHC), 27 with chronic hepatitis B, and 25 with CHC + HBCor, were examined. The personality psychological profile, reaction and personality anxiety were evaluated; the Beck inventory was used to identify borderline mental disorders. The test developed by the Karelian Research Center, Russian Academy of Medical Sciences, modified by Ya. M. Rutgaizer, and the Nottingham Health Profile were applied to estimate QL indices. RESULTS: Parameters characterizing the social and personality indices of life, such as qualitative performance of paid work, participation in social life, impossibility of adequate rest, and sexual life are most frequently influenced. The main indicators of worse QL were diminished vitality (vital energy), sleep disorders, and emergence of emotional reactions. This was largely seen in patients with active CVH infection and in those who had isolated HBcor antibodies. CONCLUSION: QL is directly related to the duration of viral infection.

[Disturbed brain bioelectric activity in patients with liver encephalopathy and cirrhosis].

Brain bioelectric activity in 52 patients with liver cirrhosis (LC) was measured with respect to the degree of hepatic encephalopathy (HE) from the results of background and reactive EEG using West Haven criteria. As the severity of LC increased, signs of HE on background EEG appeared, index frequency and a-rhythm decreased and its amplitude increased. Reactive EEG was indicative of reduced duration, intensity, and decrement rate of responses to orientational loading (visual, somatosensorial, and auditory evoked potentials). It is concluded that EEG studies permit to predict dynamics of LC clinical course and may be used as an additional diagnostic tool, especially at the preclinical stage of HE.

Serotonin metabolism parameters in patients with chronic hepatitis and liver cirrhosis.

We studied disorders in serotonin metabolism in patients with chronic hepatitis and cirrhosis of the liver with and without inflammatory process (cytolysis syndrome) and their impact for the formation of depressive disorders. Blood serotonin content decreased in patients with cirrhosis of the liver with pronounced depressive disorders. Serum serotonin level was elevated in all patients with the cytolysis syndrome.

[The diagnostic value of the detection of hepatic fibrosis serum markers in chronic viral hepatitis].

The diagnostic significance of serum markers of fibrosis was investigated in 92 patients with chronic viral hepatitis (CVH) by studying the collagenolythic activity of blood, proteasic inhibitor activity, collagen metabolism products (oxyproline fraction), and fibronectin. At the same time, the patients underwent puncture biopsy of the liver, which made it possible to determine the degree of process activity and the stage of its chronization. As the degree of fibrosis grew, the collagenase serum activity increased significantly, while the alpha1-proteinase inhibitor activity fell, the content of oxyproline (its fractions) increased, and the fibronectin level decreased. Hence, the measurement of the noted parameters allows for noninvasive diagnostics of CVH stages.

[Psychovegetative disturbances in patients with chronic non-calculous cholecystitis combined with chronic opisthorchosis].

A complex clinico-instrumental, laboratory and psychological examination of 122 patients with chronic non-calculous cholecystitis (CNCC), 63 of who had chronic opisthorchosis (CO), was conducted. The controls were 33 healthy individuals. Patients with CNCC and CO had hypomotoric dyskinesia, Oddi's sphincter dysfunction, higher levels of personal anxiety and depression more often than others.

[Spectral characteristics of electrical activity of the respiratory center in brain processes in fetus and newborn rats in vitro]. / Osobennosti spektral'nykh kharakteristik élektricheskoi aktivnosti dykhatel'nogo tsentra v protsessakh mozga plodov i novorozhdennykh krys in vitro.

Power spectral analysis of inspiratory discharges of C3-C5 ventral roots in brainstem-spinal cord preparation from foetal (18 and 20 gestation days) and newborn (0-1 and 2-3 postnatal days) rats was performed. The respiratory centre perinatal development manifests itself by decreasing of respiratory rhythm variability and increasing of inspiratory burst duration. In foetal inspiratory bursts, low-frequency oscillations (1-10 Hz) dominate. In early postnatal stage, the relative power of low-frequency oscillations begin to decrease, and medium frequency oscillations (10-50 Hz) start to dominate over the inspiratory discharge. The data obtained suggests, that perinatal maturation of respiratory centre is characterised by stabilisation of the respiratory rhythm generation and developmental alteration of inspiratory activity's spectral and temporary parameters.

[The role of opisthorchiasis in development of the secondary neurocirculatory dystonia and myocardial metabolic changes]. / Rol' opistorkhoza v razvitii vtorichnoi neirotsirkuliatornoi distonii i metabolicheskikh izmenenii miokarda.

AIM: Clarification of opisthorchiasis role in development of secondary neurocirculatory dystonia (NCD) and assessment of myocardial condition in patients with chronic opisthorchiasis (CO) with consideration of the disease duration and intensity of opisthorchotic invasion. MATERIAL AND METHODS: The trial enrolled 120 patients with CO, 35 patients with cardial NSD and 33 healthy controls. RESULTS: In long history of opisthorchiasis and severe invasion, autonomic cardiovascular regulation was abnormal. If CO patients have NCD, myocardial 99mTc-pyrophosphate scintigraphy reveals diffuse metabolic lesion of the myocardium. Long-term autonomic dysregulation of the cardiovascular system in CO and absence of adequate therapy lead to formation of progressive autonomic imbalance syndrome with sympathetic hypertonicity provoking metabolic disturbances of the myocardium.